home icon user icon
Welcome to International Network for Natural Sciences | INNS Pub.
Home My Account
Submit Manuscript
double_slash
breadcumb_bg

Resistance mechanisms of Pseudomonas aeruginosa and promising strategies to combat antibiotic resistance

Paper Details

Review Paper 06/08/2024
Views (79) Download (14)
current_issue_feature_image
publication_file

Resistance mechanisms of Pseudomonas aeruginosa and promising strategies to combat antibiotic resistance

Ablassé Rouamba, Alimata Bance, Vincent Ouedraogo, Eli Compaoré, Martin Kiendrebégo
Int. J. Biosci.25( 2), 136-145, August 2024.
Certificate: IJB 2024 [Generate Certificate]
Key: Antibiotic resistanceBiofilmPseudomonas aeruginosaQuorum sensing

Abstract

Nowadays, antibiotic resistance constitutes one of the world-wide health crisis, food security and development. This review was designed to highlight the resistance mechanisms in Pseudomonas aeruginosa, a multi-resistant bacterium, and to propose strategies to combat antibiotic resistance.  P. aeruginosa  is a Gram-negative bacillus, strict aerobic and non-fermentative. It is involved in opportunistic infections, mainly in a nosocomial context. This bacterium is characterized by a natural resistance to many antibiotics, limiting the number of effective therapies. Acquisition of resistance to β-lactams is common and results from mutations leading to overproduction of chromosomal cephalosporinase (class C β-lactamase), overexpression of active efflux systems, decreased membrane permeability and/or of the acquisition of transferable genes. Resistance to aminoglycosides is common and most often the result of the acquisition of genes for modifying enzymes. Resistance to fluoroquinolones is frequently linked to mutations in genes encoding deoxyribonucleic acid (DNA) gyrase. Overexpression of efflux pumps also contributes to resistance to aminoglycosides and fluoroquinolones. A new molecule, ceftolozane-tazobactam, appears promising, particularly in the treatment of P. aeruginosa infections overproducing the cephalosporinase AmpC. However, multi-resistant or toto-resistant strains are being described more and more frequently throughout the world. The formation of biofilm controlled by the quorum sensing enhances the antibiotic resistance in P. aeruginosa. The increase of the antibiotic resistance in P. aeruginosa is a worrying phenomenon and biologists must be aware. New promising strategies must be developed for combating P. aeruginosa  drug resistance.

VIEWS 26
Cover PDF

Aceves-Soto MP, González-Valdez A, Cocotl-Yañez M, Soberón-Chávez G. 2022. Pseudomonas aeruginosa LasR overexpression leads to a independent pyocyanin production inhibition in a low phosphate condition. Microbiology 168, 1–8. https://doi.org/10.1099/mic.0.001262

Alfiniyah C, Bees MA, Wood JA. 2019. Quorum machinery: Effect of the las system in rhl regulation of P. aeruginosa. AIP Conference Proceedings 2192, 1–12. https://doi.org/10.1063/1.5139147

Balfour-Lynn IM. 2021. Environmental risks of Pseudomonas aeruginosa – What to advise patients and parents. Journal of Cystic Fibrosis 20(1), 17–24. https://doi.org/10.1016/j.jcf.2020.12.005

Barnier J, Meyer J, Kolappan S, Gesbert G, Jamet A, Frapy E. 2022. The minor pilin PilV provides a conserved adhesion site throughout the antigenically variable meningococcal type IV pilus. Proceedings of the National Academy of Sciences of the United States of America 118(45), 1–63.

Bouteiller M, Dupont C, Bourigault Y, Latour X, Barbey C, Konto-Ghiorghi Y. 2021. Pseudomonas flagella: Generalities and specificities. International Journal of Molecular Sciences 22(7), 1–28. https://doi.org/10.3390/ijms22073337

Caroff M, Novikov A. 2020. Lipopolysaccharides: structure, function and bacterial identification. Oilseeds and fats Crops and Lipids 27(31), 1–10. https://doi.org/10.1051/ocl/2020025

Chadha J, Harjai K, Chhibber S. 2022. Revisiting the virulence hallmarks of Pseudomonas aeruginosa: a chronicle through the perspective of quorum sensing. Environmental Microbiology 24(6), 2630–2656. https://doi.org/10.1111/1462-2920.15784

Chakraborty S, Bashir Y, Sirotiya V, Ahirwar A, Das S, Vinayak V. 2023. Role of bacterial quorum sensing and quenching mechanism in the efficient operation of microbial electrochemical technologies: A state-of-the-art review. Heliyon 9(5), 1–14. https://doi.org/10.1016/j.heliyon.2023.e16205

Chimi LY, Noubom M, Bisso BN, Njateng SSG, Dzoyem JP. 2024. Biofilm Formation, Pyocyanin Production, and Antibiotic Resistance Profile of Pseudomonas aeruginosa Isolates from Wounds. International Journal of Microbiology 2024, 1–10. https://doi.org/10.1155/2024/1207536

Choi U, Lee C. 2019. Distinct Roles of Outer Membrane Porins in Antibiotic Resistance and Membrane Integrity in Escherichia coli. Frontiers in Microbiology 10, 1–9. https://doi.org/10.3389/fmicb.2019.00953

Cigana C, Castandet J, Sprynski N, Melessike M, Beyria L, Ranucci S. 2021. Pseudomonas aeruginosa Elastase Contributes to the Establishment of Chronic Lung Colonization and Modulates the Immune Response in a Murine Model. Frontiers in Microbiology 11, 1–8. https://doi.org/10.3389/fmicb.2020.620819

Diggle SP, Whiteley M. 2020. Microbe profile: Pseudomonas aeruginosa: opportunistic pathogen and lab rat. Microbiology 166(1), 30–33. https://doi.org/10.1099/mic.0.000860

Elnegery AA, Mowafy WK, Zahra TA, El-Khier NTA. 2021. Study of quorum-sensing LasR and RhlR genes and their dependent virulence factors in Pseudomonas aeruginosa isolates from infected burn wounds. Access Microbiology 3, 1–11. https://doi.org/10.1099/acmi.0.000211

Foulkes DM, McLean K, Haneef AS, Fernig DG, Winstanley C, Berry N. 2019. Pseudomonas aeruginosa Toxin ExoU as a therapeutic target in the treatment of bacterial infections. Microorganisms 7(707), 1–17. https://doi.org/10.3390/microorganisms7120707

Gholami A, Minai-Tehrani D, Mahdizadeh SJ, Saenz-Mendez P, Eriksson LA. 2023. Structural insights into Pseudomonas aeruginosa Exotoxin A–Elongation Factor 2 interactions: a molecular dynamics study. Journal of Chemical Information and Modeling 63, 1578–1591. https://doi.org/10.1021/acs.jcim.3c00064

Ghssein G, Ezzeddine Z. 2022. A review of Pseudomonas aeruginosa metallophores: Pyoverdine, Pyochelin, and Pseudopaline. Biology 11(1711), 1–18. https://doi.org/10.3390/biology11121711

Goo E, An JH, Kang Y, Hwang I. 2015. Control of bacterial metabolism by quorum sensing. Trends in Microbiology 23(9), 567–576. https://doi.org/10.1016/j.tim.2015.05.007

Huszczynski SM, Lam JS, Khursigara CM. 2020. The role of Pseudomonas aeruginosa lipopolysaccharide in bacterial pathogenesis and physiology. Pathogens 9(6), 1–22. https://doi.org/10.3390/pathogens9010006

Javanmardi F, Emami A, Pirbonyeh N, Keshavarzi A, Mahrokh R. 2019. A systematic review and meta-analysis on Exo-toxins prevalence in hospital-acquired Pseudomonas aeruginosa isolates. Infection, Genetics and Evolution 75, 1–10. https://doi.org/10.1016/j.meegid.2019.104037

Jurado-Mart I, Sainz-Mej M, McClean S. 2021. Pseudomonas aeruginosa: An audacious pathogen with an adaptable arsenal of virulence factors. International Journal of Molecular Sciences 22(3128), 1–35. https://doi.org/10.3390/ijms22063128

Kiratisin P, Tucker KD, Passador L. 2002. LasR, a transcriptional activator of Pseudomonas aeruginosa virulence genes, functions as a multimer. Journal of Bacteriology 184(17), 4912–4919. https://doi.org/10.1128/JB.184.17.4912

Kumar L, Kumar SP, Kharga K, Kumar R, Kumar P, Pandohee J. 2022. Molecular mechanisms and applications of N-acyl homoserine lactone-mediated quorum sensing in bacteria. Molecules 27, 1–28. https://doi.org/10.3390/molecules27217584

Leighton TL, Buensuceso RN, Howell PL, Burrows LL. 2015. Biogenesis of Pseudomonas aeruginosa type IV pili and regulation of their function. Environmental Microbiology 17(11), 4148–4163. https://doi.org/10.1111/1462-2920.12849

Litwin A, Rojek S, Gozdzik W, Duszynska W. 2021. Pseudomonas aeruginosa device-associated–healthcare-associated infections and its multidrug resistance at an intensive care unit of University Hospital: a Polish, 8.5-year, prospective, single-centre study. BMC Infectious Diseases 21(180), 4–11. https://doi.org/10.1186/s12879-021-05883-5

Lorusso AB, Carrara JA, Barroso CD, Tuon FF, Faoro H. 2022. Role of efflux pumps on antimicrobial resistance in Pseudomonas aeruginosa. International Journal of Molecular Sciences 23(24), 1–21. https://doi.org/10.3390/ijms232415779

Lovewell RR, Hayes SM, O’Toole GA, Berwin B. 2014. Pseudomonas aeruginosa flagellar motility activates the phagocyte PI3K/Akt pathway to induce phagocytic engulfment. American Journal of Physiology, Lung Cell and Molecular Physiology 306(14), 698–707. https://doi.org/10.1152/ajplung.00319.2013

Meletis G, Exindari M, Vavatsi N, Sofianou D, Diza E. 2012. Mechanisms responsible for the emergence of carbapenem resistance in Pseudomonas aeruginosa. Hippokratia 16(4), 303–307.

Michalska M, Wolf P. 2015. Pseudomonas Exotoxin A: optimized by evolution for effective killing. Frontiers in Microbiology 6, 1–7. https://doi.org/10.3389/fmicb.2015.00963

Morrow KA, Frank DW, Balczon R, Stevens T. 2017. The Pseudomonas aeruginosa Exoenzyme Y: A promiscuous nucleotidyl cyclase edema factor and virulence determinant. Handbook of Experimental Pharmacology 238, 67–85. https://doi.org/10.1007/164

Nadar S, Khan T, Patching SG, Omri A. 2022. Development of antibiofilm therapeutic strategies to overcome antimicrobial drug resistance. Microorganisms 10(303), 1–28. https://doi.org/10.3390/microorganisms10020303

Nordmann P, Naas T, Poirel L. 2011. Global spread of carbapenemase-producing Enterobacteriaceae. Emerging Infectious Diseases 17(10), 1791–1798. https://doi.org/10.3201/eid1710.110655

Ochsner UR, Reiser J, Fiechter A, Witholt B. 1995. Production of Pseudomonas aeruginosa rhamnolipid biosurfactants in heterologous hosts. Applied and Environmental Microbiology 61(9), 3503–3506.

Oni O, Orok E, Lawal Z, Ojo T, Oluwadare T, Bamitale T. 2023. Knowledge and perception of nosocomial infections among patients in a Nigerian hospital. Scientific Reports 13, 1–9. https://doi.org/10.1038/s41598-023-47661-0

Pachori P, Gothalwal R, Gandhi P. 2019. Emergence of antibiotic-resistant Pseudomonas aeruginosa in intensive care units: A critical review. Genes & Diseases 6(2), 109–119. https://doi.org/10.1016/j.gendis.2019.04.001

Panahi Z, Owrang M, Goli HR. 2024. Significant role of pyocyanin and exotoxin A in the pathogenesis of Pseudomonas aeruginosa isolated from hospitalized patients. Folia Medica 66(1), 88–96. https://doi.org/10.3897/folmed.66.e111038

Pang Z, Raudonis R, Glick BR, Lin T, Cheng Z. 2019. Antibiotic resistance in Pseudomonas aeruginosa: Mechanisms and alternative therapeutic strategies. Biotechnology Advances 37(1), 177–192. https://doi.org/10.1016/j.biotechadv.2018.11.013

Pereira TD, Groleau M, Déziel E. 2023. Surface growth of Pseudomonas aeruginosa reveals a regulatory effect of 3-oxo-C12-homoserine lactone in the absence of its cognate receptor, LasR. American Society for Microbiology 14(5), 1–19. https://doi.org/10.1128/mbio.00922-23

Phan S, Feng CH, Huang R, Lee ZX, Moua Y, Phung OJ, Lenhard JR. 2023. Relative abundance and detection of Pseudomonas aeruginosa from chronic wound infections globally. Microorganisms 11(1210), 1–14. https://doi.org/10.3390/microorganisms11051210

Qin S, Xiao W, Zhou C, Pu Q, Deng X, Lan L. 2022. Pseudomonas aeruginosa: Pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances, and emerging therapeutics. Signal Transduction and Targeted Therapy 7(199), 1–27. https://doi.org/10.1038/s41392-022-01056-1

Rivera-Villegas HO, Martinez-Guerra BA, Garcia-Couturier R, Xancal-Salvador LF, Esteban-Kenel V, Jaimes-Aquino RA. 2023. Predictors of mortality in patients with infections due to carbapenem-resistant Gram-negative bacteria. Antibiotics 19(1130), 1–12. https://doi.org/10.3390/antibiotics12071130

Rowe WJ, Lebman DA, Ohman DE. 2023. Mechanism of resistance to phagocytosis and pulmonary persistence in mucoid Pseudomonas aeruginosa. Frontiers in Cellular and Infection Microbiology 13, 1–13. https://doi.org/10.3389/fcimb.2023.1125901

Ruimy R, Andremont A. 2004. Quorum sensing in Pseudomonas aeruginosa: Molecular mechanism, clinical impact, and inhibition. Réanimation 13, 176–184. https://doi.org/10.1016/j.reaurg.2004.02.003

Salinas C, Florentin G, Rodriguez F, Alvarenga N, Guillen R. 2022. Terpene combinations inhibit biofilm formation in Staphylococcus aureus by interfering with initial adhesion. Microorganismes 10(1527), 1–11.

Scoffone VC, Trespidi G, Barbieri G, Irudal S, Perrin E, Buroni S. 2021. Role of RND efflux pumps in drug resistance of cystic fibrosis pathogens. Antibiotics 10(863), 1–25. https://doi.org/10.3390/antibiotics10070863

Sharma S, Mohler J, Mahajan SD, Schwartz SA, Bruggemann L, Aalinkeel R. 2023. Microbial biofilm: A review on formation, infection, antibiotic resistance, control measures, and innovative treatment. Microorganisms 11(1614), 1–32. https://doi.org/10.3390/microorganisms11061614

Song D, Meng J, Cheng J, Fan Z, Chen P, Ruan H. 2019. Pseudomonas aeruginosa quorum-sensing metabolite induces host immune cell death through cell surface lipid domain dissolution. Nature Microbiology 4, 97–111. https://doi.org/10.1038/s41564-018-0290-8

Taggar G, Rheman MA, Boerlin P, Diarra MS. 2020. Molecular epidemiology of carbapenemases in Enterobacteriales from humans, animals, food, and the environment. Antibiotics 9(693), 1–21.

Taye ZW, Abebil YA, Akalu TY, Tessema GM, Taye EB. 2023. Incidence and determinants of nosocomial infection among hospital-admitted adult chronic disease patients in University of Gondar Comprehensive Specialized Hospital, North-West Ethiopia, 2016-2020. Frontiers in Public Health 11, 1–11. https://doi.org/10.3389/fpubh.2023.1087407

Tooke CL, Hinchliffe P, Bragginton EC, Colenso CK, Hirvonen VH, Takebayashi Y. 2019. β-Lactamases and β-lactamase inhibitors in the 21st century. Journal of Molecular Biology 431(18), 3472–3500. https://doi.org/10.1016/j.jmb.2019.04.002

Tuon FF, Dantas LR, Suss PH, Ribeiro TS. 2022. Pathogenesis of the Pseudomonas aeruginosa biofilm: A review. Pathogens 11(300), 1–19. https://doi.org/10.3390/pathogens11030300

Valentin JD, Straub H, Pietsch F, Lemare M, Ahrens CH, Schreiber F. 2022. Role of the flagellar hook in the structural development and antibiotic tolerance of Pseudomonas aeruginosa biofilms. The ISME Journal 16, 1176–1186. https://doi.org/10.1038/s41396-021-01157-9

Voulgaridou G, Mantso T, Anestopoulos I, Klavaris A, Katzastra C, Kiousi D. 2021. Toxicity profiling of biosurfactants produced by novel marine bacterial strains. International Journal of Molecular Sciences 22(2383), 1–15. https://doi.org/10.3390/ijms22052383

Wagner S, Grin I, Malmsheimer S, Singh N, Torres-Vargas CE, Westerhausen S. 2018. Bacterial type III secretion systems: A complex device for the delivery of bacterial effector proteins into eukaryotic host cells. FEMS Microbiology Letters 365, 1–13. https://doi.org/10.1093/femsle/fny201

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), 1–33. https://doi.org/10.3390/cells12010195

Xie B, Wei X, Wan C, Zhao W, Song R, Xin S. 2024. Exploring the biological pathways of siderophores and their multidisciplinary applications: A comprehensive review. Molecules 29(2318), 1–19. https://doi.org/10.3390/molecules29102318

Zubair M, Ashraf M, Raza M, Mustafa B, Ahsan A. 2017. Formation and significance of bacterial biofilms. International Journal of Current Microbiology and Applied Sciences 3(12), 917–923.

Submit Manuscript