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Identification and impact on Pseudomonas aeruginosa virulence of mutations conferring resistance to a phage cocktail for phage therapy.

ABSTRACT:

Importance

In this work, we identified the putative receptors of 16 Pseudomonas phages and evaluated how resistance to phages recognizing different bacterial receptors may affect the virulence. Our findings are relevant for the implementation of phage therapy of Pseudomonas aeruginosa infections, which are difficult to treat with antibiotics. Overall, our results highlight the need to modify natural phages to enlarge the repertoire of receptors exploited by therapeutic phages and suggest that phages using the PAO1-type T4P as receptor may have limited value for the therapy of the cystic fibrosis infection.

SUBMITTER: Forti F

PROVIDER: S-EPMC10714927 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Identification and impact on <i>Pseudomonas aeruginosa</i> virulence of mutations conferring resistance to a phage cocktail for phage therapy.

Forti Francesca F Bertoli Claudia C Cafora Marco M Gilardi Sara S Pistocchi Anna A Briani Federica F

Microbiology spectrum 20231115 6

<h4>Importance</h4>In this work, we identified the putative receptors of 16 <i>Pseudomonas</i> phages and evaluated how resistance to phages recognizing different bacterial receptors may affect the virulence. Our findings are relevant for the implementation of phage therapy of <i>Pseudomonas aeruginosa</i> infections, which are difficult to treat with antibiotics. Overall, our results highlight the need to modify natural phages to enlarge the repertoire of receptors exploited by therapeutic phag ...[more]

PMID: 37966242

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Project description:IntroductionPatients with nosocomial infections are at risk of multidrug-resistant (MDR) Pseudomonas aeruginosa since these bacteria slow down the entire treatment process, increasing the morbidity and mortality of patients staying in hospital. The purpose of the research was to assess the simultaneous presence of multidrug resistance and virulence factors among nosocomial strains of P. aeruginosa to evaluate significant association among them.MethodsOne hundred and eight clinical isolates of P. aeruginosa were found in a variety of samples taken from patients having nosocomial infection, including wound swabs, pus, sputum, tracheal aspirate, and urine. An antibiogram was performed to investigate the pathogen's antibiotic sensitivity pattern against 14 widely used antibiotics in Bangladesh. Virulence factors were evaluated, and the presence of ten β-lactamase and six virulence genes was analyzed by performing PCR. By using a binary logistic regression test with a 95% confidence interval, the relationship between MDR phenotypes and the virulence attributes was assessed.ResultsThe susceptibility rate among the isolates was 70-75% for aminoglycosides (amikacin, gentamicin, netilmicin), 15-20% for cephalosporins (ceftazidime, ceftriaxone), 30-35% for quinolones (ciprofloxacin, levofloxacin), 10-15% for tetracyclines (tigecycline, doxycycline), 15-20% for carbapenem (meropenem), 10-15% for sulfonamide (co-trimoxazole), 5-10% for amoxiclav, and 30-35% for piperacillin/tazobactam. A total of 74.1% of the strains carried metallo-β-lactamase (MBL) genes. Among the isolates, 89% showed hemolytic activity, 80-90% produced different pigments such as fluorescein and pyoverdine, 46% were strong biofilm producers, and all the isolates presented different types of motilities (swimming, swarming, and twitching). The virulence genes (lasB, exoS, toxA, aprA, algD, and plcH) were detected within a range of 60-80% of the isolates.DiscussionOnly the toxA gene and twitching motility showed a significant correlation (p-value = 0.001 and 0.028, respectively) with multidrug resistance in the clinical P. aeruginosa isolates which indicates that it can be used as a drug target to combat these organisms. The high prevalence of MDR strains and their association with virulence factors revealed the potential of the pathogen to cause an infection. The current study advocates for immediate epidemiological surveillance of MDR P. aeruginosa strains in Bangladesh to impede the rapid dissemination of this opportunistic pathogen.