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Comparative study of antibiotic resistance and virulence profiles of exoU and exoS Pseudomonas aeruginosa isolates from urinary tract infections and microbial keratitis in Bangladesh and India.

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Title: Comparative study of antibiotic resistance and virulence profiles of exoU and exoS Pseudomonas aeruginosa isolates from urinary tract infections and microbial keratitis in Bangladesh and India.
Authors: Akter T; School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales (UNSW), Sydney, NSW, 2052, Australia. t.akter@unsw.edu.au.; Microbial Biotechnology Division, National Institute of Biotechnology (NIB), Dhaka, 1349, Bangladesh. t.akter@unsw.edu.au., Islam S; Department of Biotechnology, Faculty of Natural Science, Norwegian University of Science and Technology, Trondheim, 7034, Norway., Haider AM; Department of Microbiology, Primeasia University, Banani, Dhaka, 1213, Bangladesh., Ahmed R; Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, 7034, Norway., Fatema K; Department of Microbiology, Primeasia University, Banani, Dhaka, 1213, Bangladesh., Hoque MM; Department of Microbiology, Primeasia University, Banani, Dhaka, 1213, Bangladesh., Stapleton F; School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales (UNSW), Sydney, NSW, 2052, Australia., Willcox M; School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales (UNSW), Sydney, NSW, 2052, Australia.
Source: World journal of microbiology & biotechnology [World J Microbiol Biotechnol] 2026 Oct 12; Vol. 42 (10). Date of Electronic Publication: 2026 Oct 12.
Publication Type: Journal Article; Comparative Study
Language: English
Journal Info: Publisher: Springer Country of Publication: Germany NLM ID: 9012472 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-0972 (Electronic) Linking ISSN: 09593993 NLM ISO Abbreviation: World J Microbiol Biotechnol Subsets: MEDLINE
Imprint Name(s): Publication: 2005- : Berlin : Springer
Original Publication: Oxford, OX, UK : Published by Rapid Communications of Oxford Ltd in association with UNESCO and in collaboration with the International Union of Microbiological Societies, c1990-
MeSH Terms: Urinary Tract Infections*/microbiology , Pseudomonas aeruginosa*/drug effects , Pseudomonas aeruginosa*/genetics , Pseudomonas aeruginosa*/pathogenicity , Pseudomonas aeruginosa*/isolation & purification , Pseudomonas Infections*/microbiology , Keratitis*/microbiology , Drug Resistance, Bacterial*/genetics , Bacterial Proteins*/genetics , Bacterial Toxins*/genetics, Anti-Bacterial Agents/pharmacology ; Virulence Factors/genetics ; Virulence/genetics ; Ciprofloxacin/pharmacology ; Drug Resistance, Multiple, Bacterial/genetics ; Levofloxacin/pharmacology ; Humans ; Bangladesh ; India ; Microbial Sensitivity Tests ; Whole Genome Sequencing ; Pseudomonas aeruginosa Exotoxin A ; Mutation ; Genome, Bacterial
Abstract: Pseudomonas aeruginosa is an important opportunistic pathogen in urinary tract infections (UTIs) and microbial keratitis (MK), but differences in resistance and virulence between exoU and exoS P. aeruginosa isolates across regions and infection sites remain poorly understood. This study compared antibiotic resistance and virulence profiles of exoU and exoS P. aeruginosa isolates from Bangladeshi and Indian UTIs, and from Indian UTIs and MK collections. A total of 23 Bangladeshi UTI isolates were analyzed by broth microdilution for susceptibility to ciprofloxacin, levofloxacin, gentamicin, and tobramycin, and by whole-genome sequencing (WGS) to identify resistance-associated mutations, acquired resistance genes, and virulence factors. These WGS data were compared with 15 publicly available Indian UTI genomes, while the Indian UTI genomes were compared with 19 publicly available Indian MK genomes. In the Bangladeshi UTI cohort, exoU isolates showed greater resistance to fluoroquinolones and aminoglycosides than exoS isolates. Comparative analysis of Bangladeshi versus Indian UTI isolates and Indian UTI versus MK isolates showed that exoU isolates carried a burden of resistance mutations, including enrichment of GyrA Thr83Ile, ParE Asp533Glu, MexR Val126Glu, MexB Ser1041Glu, and MexC Ala262Glu. Aminoglycoside-associated substitutions FusA2 Gln161Leu and ParR Leu153Arg and Ser170Asn were more common in exoU UTI isolates. Acquired resistance genes showed aac(6')-II and aac(3)-Id were linked to Bangladeshi UTI, rmtF associated with Indian UTI, and crpP confined to MK exoU isolates. Virulence profiling showed exoU enrichment in pldA, pvdY, and csrA, whereas exoS was associated with pilC, pilV, pilW, pilY2, and pilA. Collectively, these results indicate that exoU and exoS isolates differ in both their resistance and virulence profiles, while also showing evidence of geographic and infection-site-specific adaptation.
(© 2026. The Author(s).)
Competing Interests: Declarations. Ethics approval: Not applicable. Competing interests: The authors declare no competing interests.
References: Abedin MZ, Koly FA, Aktar MB, Islam MI, Rahaman MA, Arfat ME, Farnaz N-EK, Quruni MO, Chowdhury SH, Hasan R, Shathi JH, Ahmed AA (2022) Prevalence and Antimicrobial Susceptibility Pattern of Pathogens Isolated from Different Age Groups with Urinary Tract Infection at Tangail, Bangladesh. SSR Inst Int J Life Sci 8:3044–3052. https://doi.org/10.21276/ssr-iijls.2022.8.4.2. (PMID: 10.21276/ssr-iijls.2022.8.4.2)
Akter T, Fatema K, Alam M, Parvez M, Nahar S, Uddin M, Pervin S, Farzana T (2016) Investigation of Urine Samples for Isolation, Identification and Antibiotic Susceptibility Analysis of Bacterial Pathogens from Suspected Urinary Tract Infected Patients of Bangladesh. Br J Med Med Res 18:1–10. https://doi.org/10.9734/bjmmr/2016/28576. (PMID: 10.9734/bjmmr/2016/28576)
Akter T, Stapleton F, Willcox M (2025) Differences in antimicrobial resistance between exoU and exoS isolates of Pseudomonas aeruginosa. Eur J Clin Microbiol Infect Dis 44:1629–1641. https://doi.org/10.1007/s10096-025-05132-6. (PMID: 10.1007/s10096-025-05132-64026154612241228)
Akter T, Challita PM, Haider AM, Islam S, Fatema K, Stapleton F, Willcox M (2026a) Structural and functional insights into Pseudomonas aeruginosa’s secretion systems 1–6: regulation, role in microbial keratitis and drug targets. Eur J Clin Microbiol Infect Dis 45:79–101. https://doi.org/10.1007/s10096-025-05295-2. (PMID: 10.1007/s10096-025-05295-241108437)
Akter T, Haider AM, Stapleton F, Willcox M (2026b) Differential Possession of Type 6 Secretion System Effector Genes in exoU and exoS Pseudomonas aeruginosa in Microbial Keratitis. Exp Eye Res 265:110868. https://doi.org/10.1016/j.exer.2026.110868. (PMID: 10.1016/j.exer.2026.11086841548832)
Akter T, Islam S, Haider AM, Fatema K, Stapleton F, Willcox M (2026c) Antibiotic resistance mechanisms and global resistance patterns of Pseudomonas aeruginosa in microbial keratitis. Eur J Clin Microbiol Infect Dis 45:1867–1890. https://doi.org/10.1007/s10096-026-05484-7. (PMID: 10.1007/s10096-026-05484-74187243313328337)
Akter T, Stapleton F, Ireland J, Willcox M (2026d) Comparison of virulence factor genes between exoU- and exoS-positive Pseudomonas aeruginosa isolates from microbial keratitis. Eur J Clin Microbiol Infect Dis 45:641–649. https://doi.org/10.1007/s10096-025-05294-3. (PMID: 10.1007/s10096-025-05294-341212467)
Allewelt M, Coleman FT, Grout M, Priebe GP, Pier GB (2000) Acquisition of expression of the Pseudomonas aeruginosa ExoU cytotoxin leads to increased bacterial virulence in a murine model of acute pneumonia and systemic spread. Infect Immun 68:3998–4004. https://doi.org/10.1128/IAI.68.7.3998-4004.2000. (PMID: 10.1128/IAI.68.7.3998-4004.200010858214101680)
Allsopp LP, Wood TE, Howard SA, Maggiorelli F, Nolan LM, Wettstadt S, Filloux A (2017) RsmA and AmrZ orchestrate the assembly of all three type VI secretion systems in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 114:7707–7712. https://doi.org/10.1073/pnas.1700286114. (PMID: 10.1073/pnas.1700286114286739995530658)
Andrews S (2010) FastQC: a quality control tool for high throughput sequence data. Version v0.12.1. Available at: https://www.bioinformatics.babraham.ac.uk/projects/fastqc (accessed January 2025).
Arabameri N, Heshmatipour Z, Eftekhar Ardebili S, Jafari Bidhendi Z (2021) The role of Gene Mutations (gyrA, parC) in Resistance to Ciprofloxacin in Clinical Isolates of Pseudomonas aeruginosa. Iran J Pathol 16:426–432. https://doi.org/10.30699/IJP.2021.520570.2542. (PMID: 10.30699/IJP.2021.520570.2542345671928463757)
Arefin MS, Mitu MJ, Mitu SY, Nurjahan A, Mobin M, Nahar S, Anjum H, Rahman MH (2025) Mutational alterations in the QRDR regions associated with fluoroquinolone resistance in Pseudomonas aeruginosa of clinical origin from Savar, Dhaka. PLoS ONE 20:e0302352. https://doi.org/10.1371/journal.pone.0302352. (PMID: 10.1371/journal.pone.03023523999301912002805)
Arun K, Georgoudis P (2024) Pseudomonas Keratitis: From Diagnosis to Successful Deep Anterior Lamellar Keratoplasty. Cureus 16:e56154. https://doi.org/10.7759/cureus.56154. (PMID: 10.7759/cureus.561543849596810940118)
Atassi G, Medernach R, Scheetz M, Nozick S, Rhodes NJ, Murphy-Belcaster M, Murphy KR, Alisoltani A, Ozer EA, Hauser AR (2023) Genomics of Aminoglycoside Resistance in Pseudomonas aeruginosa Bloodstream Infections at a United States Academic Hospital. Microbiol Spectr 11:e05087–e05022. https://doi.org/10.1128/spectrum.05087-22. (PMID: 10.1128/spectrum.05087-223719151710269721)
Badger-Emeka L, Emeka P, Thirugnanasambantham K, Alatawi AS (2024) The Role of Pseudomonas aeruginosa in the Pathogenesis of Corneal Ulcer, Its Associated Virulence Factors, and Suggested Novel Treatment Approaches. Pharmaceutics 16:1074. https://doi.org/10.3390/pharmaceutics16081074. (PMID: 10.3390/pharmaceutics160810743920441911360345)
Bhargava K, Nath G, Bhargava A, Kumari R, Aseri GK, Jain N (2022) Bacterial profile and antibiotic susceptibility pattern of uropathogens causing urinary tract infection in the eastern part of Northern India. Front Microbiol 13:965053. https://doi.org/10.3389/fmicb.2022.965053. (PMID: 10.3389/fmicb.2022.965053360167769396120)
Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30:2114–2120. https://doi.org/10.1093/bioinformatics/btu170. (PMID: 10.1093/bioinformatics/btu170246954044103590)
Bonneau A, Roche B, Schalk IJ (2020) Iron acquisition in Pseudomonas aeruginosa by the siderophore pyoverdine: an intricate interacting network including periplasmic and membrane proteins. Sci Rep 10:120. https://doi.org/10.1038/s41598-019-56913-x. (PMID: 10.1038/s41598-019-56913-x319248506954188)
Bortolaia V, Kaas RS, Ruppe E, Roberts MC, Schwarz S, Cattoir V, Philippon A, Allesoe RL, Rebelo AR, Florensa AF, Fagelhauer L, Chakraborty T, Neumann B, Werner G, Bender JK, Stingl K, Nguyen M, Coppens J, Xavier BB, Malhotra-Kumar S, Westh H, Pinholt M, Anjum MF, Duggett NA, Kempf I, Nykäsenoja S, Olkkola S, Wieczorek K, Amaro A, Clemente L, Mossong J, Losch S, Ragimbeau C, Lund O, Aarestrup FM (2020) ResFinder 4.0 for predictions of phenotypes from genotypes. J Antimicrob Chemother 75:3491–3500. https://doi.org/10.1093/jac/dkaa345. (PMID: 10.1093/jac/dkaa345327801127662176)
Boulant T, Boudehen YM, Filloux A, Plesiat P, Naas T, Dortet L (2018) Higher Prevalence of PldA, a Pseudomonas aeruginosa Trans-Kingdom H2-Type VI Secretion System Effector, in Clinical Isolates Responsible for Acute Infections and in Multidrug Resistant Strains. Front Microbiol 9:2578. https://doi.org/10.3389/fmicb.2018.02578. (PMID: 10.3389/fmicb.2018.02578304208476215852)
Chávez-Jacobo VM, Hernández-Ramírez KC, Romo-Rodríguez P, Pérez-Gallardo RV, Campos-García J, Gutiérrez-Corona JF, García-Merinos JP, Meza-Carmen V, Silva-Sánchez J, Ramírez-Díaz MI (2018) CrpP is a novel ciprofloxacin-modifying enzyme encoded by the Pseudomonas aeruginosa pUM505 plasmid. Antimicrob Agents Chemother 62:e02629–e02617. https://doi.org/10.1128/AAC.02629-17. (PMID: 10.1128/AAC.02629-17295811235971611)
Cho HH, Park Y (2025) Coexistence of Multidrug Resistance and Hypervirulence-Associated Genes in Clinical Carbapenem-Resistant Pseudomonas aeruginosa. J Microbiol Biotechnol 35:e2505031. https://doi.org/10.4014/jmb.2505.05031. (PMID: 10.4014/jmb.2505.050314101681812535857)
Chopra I, O’Neill AJ, Miller K (2003) The role of mutators in the emergence of antibiotic-resistant bacteria. Drug Resist Updat 6:137–145. https://doi.org/10.1016/s1368-7646(03)00041-4. (PMID: 10.1016/s1368-7646(03)00041-412860461)
Choy MH, Stapleton F, Willcox MDP, Zhu H (2008) Comparison of virulence factors in Pseudomonas aeruginosa strains isolated from contact lens- and non-contact lens-related keratitis. J Med Microbiol 57:1539–1546. https://doi.org/10.1099/jmm.0.2008/003723-0. (PMID: 10.1099/jmm.0.2008/003723-019018027)
Croucher NJ, Page AJ, Connor TR, Delaney AJ, Keane JA, Bentley SD, Parkhill J, Harris SR (2015) Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res 43:e15. https://doi.org/10.1093/nar/gku1196. (PMID: 10.1093/nar/gku119625414349)
de Bentzmann S, Plesiat P (2011) The Pseudomonas aeruginosa opportunistic pathogen and human infections. Environ Microbiol 13:1655–1665. https://doi.org/10.1111/j.1462-2920.2011.02469.x. (PMID: 10.1111/j.1462-2920.2011.02469.x21450006)
de Sousa T, Hebraud M, Alves O, Costa E, Maltez L, Pereira JE, Martins A, Igrejas G, Poeta P (2023) Study of Antimicrobial Resistance, Biofilm Formation, and Motility of Pseudomonas aeruginosa Derived from Urine Samples. Microorganisms 11:1345. https://doi.org/10.3390/microorganisms11051345. (PMID: 10.3390/microorganisms110513453731731910224020)
DGHS (2021) In: Welfare, MoHaF (eds) Standard Treatment Guidelines (STG) on Antibiotic Use in Common Infectious Diseases of Bangladesh. Directorate General of Health Services, Ministry of Health and Family Welfare 110, Bangladesh.
Dulanto Chiang A, Patil PP, Beka L, Youn JH, Launay A, Bonomo RA, Khil PP, Dekker JP (2022) Hypermutator strains of Pseudomonas aeruginosa reveal novel pathways of resistance to combinations of cephalosporin antibiotics and beta-lactamase inhibitors. PLoS Biol 20:e3001878. https://doi.org/10.1371/journal.pbio.3001878. (PMID: 10.1371/journal.pbio.3001878363994369718400)
El-Badawy MF, Eed EM, Sleem AS, El-Sheikh AAK, Maghrabi IA, Abdelwahab SF (2022) The First Saudi Report of Novel and Common Mutations in the gyrA and parC Genes Among Pseudomonas Spp. Clinical Isolates Recovered from Taif Area. Infect Drug Resist 15:3801–3814. https://doi.org/10.2147/IDR.S372027. (PMID: 10.2147/IDR.S372027358756149300750)
Elbargisy RM (2022) Characterization of Uropathogenic Pseudomonas aeruginosa: Serotypes, Resistance Phenotypes, and Virulence Genotypes. J Pure Appl Microbiol 16:1284–1297. https://doi.org/10.22207/Jpam.16.2.57. (PMID: 10.22207/Jpam.16.2.57)
Finck-Barbancon V, Goranson J, Zhu L, Sawa T, Wiener-Kronish JP, Fleiszig SM, Wu C, Mende-Mueller L, Frank DW (1997) ExoU expression by Pseudomonas aeruginosa correlates with acute cytotoxicity and epithelial injury. Mol Microbiol 25:547–557. https://doi.org/10.1046/j.1365-2958.1997.4891851.x. (PMID: 10.1046/j.1365-2958.1997.4891851.x9302017)
Firouzi-Dalvand L, Pooladi M, Nowroozi J, Akhvan-Sepahi A, Hooshiyar M (2016) Presence of exoU and exoS genes in Pseudomonas aeruginosa isolated from urinary tract infections. Infect Epidemiol Med 2:8–11. (PMID: 10.18869/modares.iem.2.2.8)
Gellatly SL, Hancock RE (2013) Pseudomonas aeruginosa: new insights into pathogenesis and host defenses. Pathog Dis 67:159–173. https://doi.org/10.1111/2049-632X.12033. (PMID: 10.1111/2049-632X.1203323620179)
Ghssein G, Ezzeddine Z (2022) A Review of Pseudomonas aeruginosa Metallophores: Pyoverdine, Pyochelin and Pseudopaline. Biology (Basel) 11:1711. https://doi.org/10.3390/biology11121711. (PMID: 10.3390/biology11121711365522209774294)
Gorgani N, Ahlbrand S, Patterson A, Pourmand N (2009) Detection of point mutations associated with antibiotic resistance in Pseudomonas aeruginosa. Int J Antimicrob Agents 34:414–418. https://doi.org/10.1016/j.ijantimicag.2009.05.013. (PMID: 10.1016/j.ijantimicag.2009.05.013196566622744841)
Gurevich A, Saveliev V, Vyahhi N, Tesler G (2013) QUAST: quality assessment tool for genome assemblies. Bioinformatics 29:1072–1075. https://doi.org/10.1093/bioinformatics/btt086. (PMID: 10.1093/bioinformatics/btt086234223393624806)
Gutierrez P, Li Y, Osborne MJ, Pomerantseva E, Liu Q, Gehring K (2005) Solution structure of the carbon storage regulator protein CsrA from Escherichia coli. J Bacteriol 187:3496–3501. https://doi.org/10.1128/JB.187.10.3496-3501.2005. (PMID: 10.1128/JB.187.10.3496-3501.2005158669371112004)
Hall KM, Williams LG, Smith RD, Kuang EA, Ernst RK, Bojanowski CM, Wimley WC, Morici LA, Pursell ZF (2025) Mutational signature analysis predicts bacterial hypermutation and multidrug resistance. Nat Commun 16:19. https://doi.org/10.1038/s41467-024-55206-w. (PMID: 10.1038/s41467-024-55206-w3974697511695600)
Hassuna NA (2016) Molecular Detection of the Virulent ExoU Genotype of Pseudomonas aeruginosa Isolated from Infected Surgical Incisions. Surg Infect 17:610–614. https://doi.org/10.1089/sur.2016.065. (PMID: 10.1089/sur.2016.065)
Hayashi N, Nishizawa H, Kitao S, Deguchi S, Nakamura T, Fujimoto A, Shikata M, Gotoh N (2015) Pseudomonas aeruginosa injects type III effector ExoS into epithelial cells through the function of type IV pili. FEBS Lett 589:890–896. https://doi.org/10.1016/j.febslet.2015.02.031. (PMID: 10.1016/j.febslet.2015.02.03125747138)
Hoang DT, Chernomor O, von Haeseler A, Minh BQ, Vinh LS (2018) UFBoot2: Improving the Ultrafast Bootstrap Approximation. Mol Biol Evol 35:518–522. https://doi.org/10.1093/molbev/msx281. (PMID: 10.1093/molbev/msx281290779045850222)
Hocquet D, Berthelot P, Roussel-Delvallez M, Favre R, Jeannot K, Bajolet O, Marty N, Grattard F, Mariani-Kurkdjian P, Bingen E, Husson MO, Couetdic G, Plesiat P (2007) Pseudomonas aeruginosa may accumulate drug resistance mechanisms without losing its ability to cause bloodstream infections. Antimicrob Agents Chemother 51:3531–3536. https://doi.org/10.1128/AAC.00503-07. (PMID: 10.1128/AAC.00503-07176821062043289)
Hooper DC, Jacoby GA (2015) Mechanisms of drug resistance: quinolone resistance. Ann N Y Acad Sci 1354:12–31. https://doi.org/10.1111/nyas.12830. (PMID: 10.1111/nyas.12830261902234626314)
Horna G, Ruiz J (2021) Type 3 secretion system of Pseudomonas aeruginosa. Microbiol Res 246:126719. https://doi.org/10.1016/j.micres.2021.126719. (PMID: 10.1016/j.micres.2021.12671933582609)
Horna G, Aida Palacios CA, Guerra H, Ruiz J (2019) High frequency of the exoU plus/exoS plus genotype associated with multidrug-resistant high-risk clones of Pseudomonas aeruginosa clinical isolates from Peruvian hospitals. Sci Rep 9:10874. https://doi.org/10.1038/s41598-019-47303-4. (PMID: 10.1038/s41598-019-47303-4313504126659710)
Idris SN, Desa MN, Aziz MN, Taib NM (2012) Antimicrobial susceptibility pattern and distribution of exoU and exoS in clinical isolates of Pseudomonas aeruginosa at a Malaysian hospital. Southeast Asian J Trop Med Public Health 43:116–123. (PMID: 23082561)
Jalal S, Ciofu O, Høiby N, Gotoh N, Wretlind B (2000) Molecular mechanisms of fluoroquinolone resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients. Antimicrob Agents Chemother 44:710–712. https://doi.org/10.1128/aac.44.3.710-712.2000. (PMID: 10.1128/aac.44.3.710-712.20001068134389751)
Jiang F, Waterfield NR, Yang J, Yang G, Jin Q (2014) A Pseudomonas aeruginosa type VI secretion phospholipase D effector targets both prokaryotic and eukaryotic cells. Cell Host Microbe 15:600–610. https://doi.org/10.1016/j.chom.2014.04.010. (PMID: 10.1016/j.chom.2014.04.01024832454)
Jolley KA, Bray JE, Maiden MC (2018) Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res 3:124. https://doi.org/10.12688/wellcomeopenres.14826.1. (PMID: 10.12688/wellcomeopenres.14826.1303453916192448)
Joseph J, Karoliya R, Sheba E, Sharma S, Bagga B, Garg P (2023) Trends in the Microbiological Spectrum of Nonviral Keratitis at a Single Tertiary Care Ophthalmic Hospital in India: A Review of 30 years. Cornea 42:837–846. https://doi.org/10.1097/ico.0000000000003105. (PMID: 10.1097/ico.000000000000310535942533)
Kalal BS, Nagaraj S (2016) Urinary tract infections: a retrospective, descriptive study of causative organisms and antimicrobial pattern of samples received for culture, from a tertiary care setting. Germs 6:132–138. https://doi.org/10.11599/germs.2016.1100. (PMID: 10.11599/germs.2016.1100280539165187754)
Khan M, Stapleton F, Summers S, Rice SA, Willcox MDP (2020) Antibiotic Resistance Characteristics of Pseudomonas aeruginosa Isolated from Keratitis in Australia and India. Antibiot (Basel) 9:600. https://doi.org/10.3390/antibiotics9090600. (PMID: 10.3390/antibiotics9090600)
Lamas Ferreiro JL, Alvarez Otero J, Gonzalez Gonzalez L, Novoa Lamazares L, Arca Blanco A, Bermudez Sanjurjo JR, Rodriguez Conde I, Fernandez Soneira M, de la Fuente Aguado J (2017) Pseudomonas aeruginosa urinary tract infections in hospitalized patients: Mortality and prognostic factors. PLoS ONE 12:e0178178. https://doi.org/10.1371/journal.pone.0178178. (PMID: 10.1371/journal.pone.0178178285529725446154)
Letunic I, Bork P (2021) Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res 49:W293–W296. https://doi.org/10.1093/nar/gkab301. (PMID: 10.1093/nar/gkab301338857858265157)
Ling TKW, Tam PC, Liu ZK, Cheng AFB (2001) Evaluation of VITEK 2 Rapid Identification and Susceptibility Testing System against Gram-Negative Clinical Isolates. J Clin Microbiol 39:2964–2966. https://doi.org/10.1128/JCM.39.8.2964-2966.2001. (PMID: 10.1128/JCM.39.8.2964-2966.20011147402388270)
López M, Rojo-Bezares B, Chichón G, Sáenz Y (2022) Resistance to fluoroquinolones in Pseudomonas aeruginosa from human, animal, food and environmental origin: the role of CrpP and mobilizable ICEs. Antibiotics 11:1271. https://doi.org/10.3390/antibiotics11091271. (PMID: 10.3390/antibiotics11091271361400509495688)
Macia MD, Blanquer D, Togores B, Sauleda J, Perez JL, Oliver A (2005) Hypermutation is a key factor in development of multiple-antimicrobial resistance in Pseudomonas aeruginosa strains causing chronic lung infections. Antimicrob Agents Chemother 49:3382–3386. https://doi.org/10.1128/AAC.49.8.3382-3386.2005. (PMID: 10.1128/AAC.49.8.3382-3386.2005160489511196247)
Marden JN, Diaz MR, Walton WG, Gode CJ, Betts L, Urbanowski ML, Redinbo MR, Yahr TL, Wolfgang MC (2013) An unusual CsrA family member operates in series with RsmA to amplify posttranscriptional responses in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 110:15055–15060. https://doi.org/10.1073/pnas.1307217110. (PMID: 10.1073/pnas.1307217110239801773773774)
Mittal R, Aggarwal S, Sharma S, Chhibber S, Harjai K (2009) Urinary tract infections caused by Pseudomonas aeruginosa: a minireview. J Infect Public Health 2:101–111. https://doi.org/10.1016/j.jiph.2009.08.003. (PMID: 10.1016/j.jiph.2009.08.00320701869)
Newman JN, Floyd RV, Fothergill JL (2022) Invasion and diversity in Pseudomonas aeruginosa urinary tract infections. J Med Microbiol 71:001458. https://doi.org/10.1099/jmm.0.001458. (PMID: 10.1099/jmm.0.001458352758069176269)
Ng PC, Henikoff S (2003) SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res 31:3812–3814. https://doi.org/10.1093/nar/gkg509. (PMID: 10.1093/nar/gkg50912824425168916)
Nieto V, Kroken AR, Grosser MR, Smith BE, Metruccio MME, Hagan P, Hallsten ME, Evans DJ, Fleiszig SMJ (2019) Type IV Pili Can Mediate Bacterial Motility within Epithelial Cells. mBio 10:e02880–e02818. https://doi.org/10.1128/mBio.02880-18. (PMID: 10.1128/mBio.02880-18314315586703432)
Obritsch MD, Fish DN, MacLaren R, Jung R (2005) Nosocomial infections due to multidrug-resistant Pseudomonas aeruginosa: epidemiology and treatment options. Pharmacotherapy 25:1353–1364. https://doi.org/10.1592/phco.2005.25.10.1353. (PMID: 10.1592/phco.2005.25.10.135316185180)
Oh H, Stenhoff J, Jalal S, Wretlind B (2003) Role of efflux pumps and mutations in genes for topoisomerases II and IV in fluoroquinolone-resistant Pseudomonas aeruginosa strains. Microb Drug Resist 9:323–328. https://doi.org/10.1089/107662903322762743. (PMID: 10.1089/10766290332276274315000738)
Oliver A, Canton R, Campo P, Baquero F, Blazquez J (2000) High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288:1251–1254. https://doi.org/10.1126/science.288.5469.1251. (PMID: 10.1126/science.288.5469.125110818002)
Page AJ, Taylor B, Delaney AJ, Soares J, Seemann T, Keane JA, Harris SR (2016) SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments. Microb Genom 2:e000056. https://doi.org/10.1099/mgen.0.000056. (PMID: 10.1099/mgen.0.000056283488515320690)
Park Y, Koo SH (2022) Epidemiology, Molecular Characteristics, and Virulence Factors of Carbapenem-Resistant Pseudomonas aeruginosa Isolated from Patients with Urinary Tract Infections. Infect Drug Resist 15:141–151. https://doi.org/10.2147/IDR.S346313. (PMID: 10.2147/IDR.S346313350586978765443)
Park MH, Kim SY, Roh EY, Lee HS (2017) Difference of Type 3 secretion system (T3SS) effector gene genotypes (exoU and exoS) and its implication to antibiotics resistances in isolates of Pseudomonas aeruginosa from chronic otitis media. Auris Nasus Larynx 44:258–265. https://doi.org/10.1016/j.anl.2016.07.005. (PMID: 10.1016/j.anl.2016.07.00527461174)
Peek ME, Bhatnagar A, McCarty NA, Zughaier SM (2012) Pyoverdine, the Major Siderophore in Pseudomonas aeruginosa, Evades NGAL Recognition. Interdiscip Perspect Infect Dis 2012:843509. https://doi.org/10.1155/2012/843509. (PMID: 10.1155/2012/843509229733073438788)
Pena C, Cabot G, Gomez-Zorrilla S, Zamorano L, Ocampo-Sosa A, Murillas J, Almirante B, Pomar V, Aguilar M, Granados A, Calbo E, Rodriguez-Bano J, Rodriguez-Lopez F, Tubau F, Martinez-Martinez L, Oliver A Spanish Network for Research in Infectious Diseases (REIPI) (2015) Influence of virulence genotype and resistance profile in the mortality of Pseudomonas aeruginosa bloodstream infections. Clin Infect Dis 60:539–548. https://doi.org/10.1093/cid/ciu866.
Phillips RM, Six DA, Dennis EA, Ghosh P (2003) In vivo phospholipase activity of the Pseudomonas aeruginosa cytotoxin ExoU and protection of mammalian cells with phospholipase A2 inhibitors. J Biol Chem 278:41326–41332. https://doi.org/10.1074/jbc.M302472200. (PMID: 10.1074/jbc.M30247220012915403)
Pinna A, Usai D, Sechi LA, Molicotti P, Zanetti S, Carta A (2008) Detection of virulence factors in Pseudomonas aeruginosa strains isolated from contact lens-associated corneal ulcers. Cornea 27:320–326. https://doi.org/10.1097/ICO.0b013e31815c5a3f. (PMID: 10.1097/ICO.0b013e31815c5a3f18362661)
Pobiega M, Maciag J, Pomorska-Wesolowska M, Chmielarczyk A, Romaniszyn D, Ziolkowski G, Heczko PB, Wojkowska-Mach J, Bulanda M (2016) Urinary tract infections caused by Pseudomonas aeruginosa among children in Southern Poland: Virulence factors and antibiotic resistance. J Pediatr Urol 12:36e1–3636. https://doi.org/10.1016/j.jpurol.2015.05.034. (PMID: 10.1016/j.jpurol.2015.05.034)
Poole K (2005) Aminoglycoside resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 49:479–487. https://doi.org/10.1128/AAC.49.2.479-487.2005. (PMID: 10.1128/AAC.49.2.479-487.200515673721547279)
Qin S, Xiao W, Zhou C, Pu Q, Deng X, Lan L, Liang H, Song X, Wu M (2022) Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics. Signal Transduct Target Ther 7:199. https://doi.org/10.1038/s41392-022-01056-1. (PMID: 10.1038/s41392-022-01056-1357526129233671)
Rahman M, Prasad KN, Pathak A, Pati BK, Singh A, Ovejero CM, Ahmad S, Gonzalez-Zorn B (2015) RmtC and RmtF 16S rRNA methyltransferase in NDM-1–producing Pseudomonas aeruginosa. Emerg Infect Dis 21:2059. https://doi.org/10.3201/eid2111.150271. (PMID: 10.3201/eid2111.150271264889374622239)
Rao L, De La Rosa I, Xu Y, Sha Y, Bhattacharya A, Holtzman MJ, Gilbert BE, Eissa NT (2021) Pseudomonas aeruginosa survives in epithelia by ExoS-mediated inhibition of autophagy and mTOR. EMBO Rep 22:e50613. https://doi.org/10.15252/embr.202050613. (PMID: 10.15252/embr.20205061333345425)
Rather PN, Munayyer H, Mann PA, Hare RS, Miller GH, Shaw KJ (1992) Genetic analysis of bacterial acetyltransferases: identification of amino acids determining the specificities of the aminoglycoside 6’-N-acetyltransferase Ib and IIa proteins. J Bacteriol 174:3196–3203. https://doi.org/10.1128/jb.174.10.3196-3203.1992. (PMID: 10.1128/jb.174.10.3196-3203.19921577689205986)
Riccio ML, Docquier JD, Dell’Amico E, Luzzaro F, Amicosante G, Rossolini GM (2003) Novel 3-N-aminoglycoside acetyltransferase gene, aac(3)-Ic, from a Pseudomonas aeruginosa integron. Antimicrob Agents Chemother 47:1746–1748. https://doi.org/10.1128/aac.47.5.1746-1748.2003.
Rojano-Nisimura AM, Grismore KB, Ruzek JS, Avila JL, Contreras LM (2024) The Post-Transcriptional Regulatory Protein CsrA Amplifies Its Targetome through Direct Interactions with Stress-Response Regulatory Hubs: The EvgA and AcnA Cases. Microorganisms 12:636. https://doi.org/10.3390/microorganisms12040636. (PMID: 10.3390/microorganisms120406363867458111052181)
Roy S, Nandy S, Morita D, Nandy RK, Veeraraghavan B, Walia K, Das S, Basu S (2026) Genomic analysis of a novel high-risk ST5217/ExoU+/O11 clone of carbapenem-resistant OXA-181- and VIM-2-producing Pseudomonas aeruginosa in India. J Glob Antimicrob Resist 46:158–161. https://doi.org/10.1016/j.jgar.2025.12.002. (PMID: 10.1016/j.jgar.2025.12.00241380995)
Russell AB, LeRoux M, Hathazi K, Agnello DM, Ishikawa T, Wiggins PA, Wai SN, Mougous JD (2013) Diverse type VI secretion phospholipases are functionally plastic antibacterial effectors. Nature 496:508–512. https://doi.org/10.1038/nature12074. (PMID: 10.1038/nature12074235528913652678)
Sabtcheva S, Galimand M, Gerbaud G, Courvalin P, Lambert T (2003) Aminoglycoside resistance gene ant(4′’)-IIb of Pseudomonas aeruginosa BM4492, a clinical isolate from Bulgaria. Antimicrob Agents Chemother 47:1584–1588. https://doi.org/10.1128/aac.47.5.1584-1588.2003. (PMID: 10.1128/aac.47.5.1584-1588.200312709326153341)
Sanjee S, Karim M, Akter T, Parvez M, Hossain M, Jannat B, Pervin S (2017) Prevalence and antibiogram of bacterial uropathogens of urinary tract infections from a tertiary care hospital of Bangladesh. J Sci Res 9:317–328. https://doi.org/10.3329/jsr.v9i3.31677. (PMID: 10.3329/jsr.v9i3.31677)
Sato H, Frank DW, Hillard CJ, Feix JB, Pankhaniya RR, Moriyama K, Finck-Barbancon V, Buchaklian A, Lei M, Long RM, Wiener-Kronish J, Sawa T (2003) The mechanism of action of the Pseudomonas aeruginosa-encoded type III cytotoxin, ExoU. EMBO J 22:2959–2969. https://doi.org/10.1093/emboj/cdg290. (PMID: 10.1093/emboj/cdg29012805211162142)
Sawa T, Shimizu M, Moriyama K, Wiener-Kronish JP (2014) Association between Pseudomonas aeruginosa type III secretion, antibiotic resistance, and clinical outcome: a review. Crit Care 18:668. https://doi.org/10.1186/s13054-014-0668-9. (PMID: 10.1186/s13054-014-0668-9256724964331484)
Schwengers O, Jelonek L, Dieckmann MA, Beyvers S, Blom J, Goesmann A (2021) Bakta: rapid and standardized annotation of bacterial genomes via alignment-free sequence identification. Microb Genom 7:000685. https://doi.org/10.1099/mgen.0.000685. (PMID: 10.1099/mgen.0.000685347393698743544)
Seemann T (2015) Snippy: fast bacterial variant calling from NGS reads. Version 4.6.0. Available at: https://github.com/tseemann/snippy (accessed January 2025).
Sharmin S, Nahar A, Alamgir F, Fahim I (2021) Prevalence and Antibiotic Sensitivity Pattern of Pseudomonas aeruginosa Isolates from Urine Samples in A Tertiary Care Hospital. Dhaka Shishu (Child). Hosp J 37:40–44. https://doi.org/10.3329/dshj.v37i1.59114. (PMID: 10.3329/dshj.v37i1.59114)
Shaver CM, Hauser AR (2004) Relative contributions of Pseudomonas aeruginosa ExoU, ExoS, and ExoT to virulence in the lung. Infect Immun 72:6969–6977. https://doi.org/10.1128/IAI.72.12.6969-6977.2004. (PMID: 10.1128/IAI.72.12.6969-6977.200415557619529154)
Shikata M, Hayashi N, Fujimoto A, Nakamura T, Matsui N, Ishiyama A, Maekawa Y, Gotoh N (2016) The pilT gene contributes to type III ExoS effector injection into epithelial cells in Pseudomonas aeruginosa. J Infect Chemother 22:216–220. https://doi.org/10.1016/j.jiac.2015.12.012. (PMID: 10.1016/j.jiac.2015.12.01226809217)
Singh RB, Singh Parmar UP, Woreta F, Srikumaran D, Sharma N, Jhanji V (2026) Global burden, risk factors, causative organisms and antibiotic susceptibility patterns in bacterial keratitis. Ocul Surf 39:49–57. https://doi.org/10.1016/j.jtos.2025.12.003. (PMID: 10.1016/j.jtos.2025.12.00341422890)
Stapleton F (2023) The epidemiology of infectious keratitis. Ocul Surf 28:351–363. https://doi.org/10.1016/j.jtos.2021.08.007. (PMID: 10.1016/j.jtos.2021.08.00734419639)
Subedi D, Vijay AK, Kohli GS, Rice SA, Willcox M (2018a) Association between possession of ExoU and antibiotic resistance in Pseudomonas aeruginosa. PLoS ONE 13:e0204936. https://doi.org/10.1371/journal.pone.0204936. (PMID: 10.1371/journal.pone.0204936302657096161911)
Subedi D, Vijay AK, Kohli GS, Rice SA, Willcox M (2018b) Comparative genomics of clinical strains of Pseudomonas aeruginosa strains isolated from different geographic sites. Sci Rep 8:15668. https://doi.org/10.1038/s41598-018-34020-7. (PMID: 10.1038/s41598-018-34020-7303530706199293)
Subedi D, Vijay AK, Kohli GS, Rice SA, Willcox M (2018c) Nucleotide sequence analysis of NPS-1 beta-lactamase and a novel integron (In1427)-carrying transposon in an MDR Pseudomonas aeruginosa keratitis strain. J Antimicrob Chemother 73:1724–1726. https://doi.org/10.1093/jac/dky073. (PMID: 10.1093/jac/dky07329547943)
Subedi D, Vijay AK, Willcox M (2018d) Overview of mechanisms of antibiotic resistance in Pseudomonas aeruginosa: an ocular perspective. Clin Exp Optom 101:162–171. https://doi.org/10.1111/cxo.12621. (PMID: 10.1111/cxo.1262129044738)
Tegenfeldt F, Kuznetsov D, Manni M, Berkeley M, Zdobnov EM, Kriventseva EV (2025) OrthoDB and BUSCO update: annotation of orthologs with wider sampling of genomes. Nucleic Acids Res 53:D516–D522. https://doi.org/10.1093/nar/gkae987. (PMID: 10.1093/nar/gkae9873953504311701741)
Thirumalmuthu K, Devarajan B, Prajna L, Mohankumar V (2019) Mechanisms of Fluoroquinolone and Aminoglycoside Resistance in Keratitis-Associated Pseudomonas aeruginosa. Microb Drug Resist 25:813–823. https://doi.org/10.1089/mdr.2018.0218. (PMID: 10.1089/mdr.2018.021830807251)
Varga JJ, Barbier M, Mulet X, Bielecki P, Bartell JA, Owings JP, Martinez-Ramos I, Hittle LE, Davis MR Jr, Damron FH, Liechti GW, Puchalka J, dos Santos VA, Ernst RK, Papin JA, Alberti S, Oliver A, Goldberg JB (2015) Genotypic and phenotypic analyses of a Pseudomonas aeruginosa chronic bronchiectasis isolate reveal differences from cystic fibrosis and laboratory strains. BMC Genomics 16:883. https://doi.org/10.1186/s12864-015-2069-0. (PMID: 10.1186/s12864-015-2069-0265191614628258)
Vaziri F, Peerayeh SN, Nejad QB, Farhadian A (2011) The prevalence of aminoglycoside-modifying enzyme genes (aac (6′)-I, aac (6′)-II, ant (2)-I, aph (3′)-VI) in Pseudomonas aeruginosa. Clin (Sao Paulo) 66:1519–1522 https://doi.org/10.1590/s1807-59322011000900002. (PMID: 10.1590/s1807-59322011000900002)
Veetilvalappil VV, Manuel A, Aranjani JM, Tawale R, Koteshwara A (2022) Pathogenic arsenal of Pseudomonas aeruginosa: an update on virulence factors. Future Microbiol 17:465–481. https://doi.org/10.2217/fmb-2021-0158. (PMID: 10.2217/fmb-2021-015835289684)
Wettstadt S, Wood TE, Fecht S, Filloux A (2019) Delivery of the Pseudomonas aeruginosa Phospholipase Effectors PldA and PldB in a VgrG- and H2-T6SS-Dependent Manner. Front Microbiol 10:1718. https://doi.org/10.3389/fmicb.2019.01718. (PMID: 10.3389/fmicb.2019.01718314175156684961)
Wick RR, Judd LM, Gorrie CL, Holt KE (2017) Unicycler: Resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput Biol 13:e1005595. https://doi.org/10.1371/journal.pcbi.1005595. (PMID: 10.1371/journal.pcbi.1005595285948275481147)
Wiegand I, Hilpert K, Hancock RE (2008) Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protoc 3:163–175. https://doi.org/10.1038/nprot.2007.521. (PMID: 10.1038/nprot.2007.52118274517)
Wilderman PJ, Vasil AI, Johnson Z, Vasil ML (2001) Genetic and biochemical analyses of a eukaryotic-like phospholipase D of Pseudomonas aeruginosa suggest horizontal acquisition and a role for persistence in a chronic pulmonary infection model. Mol Microbiol 39:291–303. https://doi.org/10.1046/j.1365-2958.2001.02282.x. (PMID: 10.1046/j.1365-2958.2001.02282.x11136451)
Wong TKF, Ly-Trong N, Ren H, Demotte P, Baños H, Roger AJ, Susko E, Bielow C, De Maio N, Goldman N, Hahn MW, dos Reis M, Vinh LS, Huttley G, Lanfear R, Minh BQ (2026) IQ-TREE 3: phylogenomic inference software using complex evolutionary models. Mol Biol Evol 43:msag117. https://doi.org/10.1093/molbev/msag117. (PMID: 10.1093/molbev/msag1174208555913191116)
Wood SJ, Goldufsky JW, Seu MY, Dorafshar AH, Shafikhani SH (2023) Pseudomonas aeruginosa Cytotoxins: Mechanisms of Cytotoxicity and Impact on Inflammatory Responses. Cells 12:195. https://doi.org/10.3390/cells12010195. (PMID: 10.3390/cells12010195366119909818787)
Zahra FA, Jabeen I, Uddin MJ, Nahar N, Islam S, Shuvo SR (2022) Genomic Analysis to Elucidate the Antibiotic Resistance Mechanism of Extremely Drug-Resistant Pseudomonas aeruginosa Strains Isolated from Bangladesh. Bioresearch Commun 9:1208–1214. https://doi.org/10.3329/brc.v9i1.63601. (PMID: 10.3329/brc.v9i1.63601)
Zhou S, Liu B, Zheng D, Chen L, Yang J (2025) VFDB 2025: an integrated resource for exploring anti-virulence compounds. Nucleic Acids Res 53:D871–D877. https://doi.org/10.1093/nar/gkae968. (PMID: 10.1093/nar/gkae9683947073811701737)
Contributed Indexing: Keywords: Pseudomonas aeruginosa; exoS; exoU; Antibiotic resistance; Microbial keratitis; Urinary tract infection; Virulence factors
Substance Nomenclature: 0 (Anti-Bacterial Agents)
0 (Virulence Factors)
0 (Bacterial Proteins)
EC 2.4.2.31 (Pseudomonas aeruginosa Exotoxin A)
5E8K9I0O4U (Ciprofloxacin)
0 (pseudomonas exoprotein A protein, Pseudomonas aeruginosa)
0 (Bacterial Toxins)
6GNT3Y5LMF (Levofloxacin)
Entry Date(s): Date Created: 20261012 Date Completed: 20261012 Latest Revision: 20261029
Update Code: 20261029
PubMed Central ID: PMC13658543
DOI: 10.1007/s11274-026-05320-2
PMID: 42862478
Database: MEDLINE
Description
ISSN:1573-0972
DOI:10.1007/s11274-026-05320-2