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Combating virulence of Gram-negative bacilli by OmpA inhibition.

ABSTRACT: Preventing the adhesion of pathogens to host cells provides an innovative approach to tackling multidrug-resistant bacteria. In this regard, the identification of outer membrane protein A (OmpA) as a key bacterial virulence factor has been a major breakthrough. The use of virtual screening helped us to identify a cyclic hexapeptide AOA-2 that inhibits the adhesion of Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli to host cells and the formation of biofilm, thereby preventing the development of infection in vitro and in a murine sepsis peritoneal model. Inhibition of OmpA offers a strategy as monotherapy to address the urgent need for treatments for infections caused by Gram-negative bacilli.

SUBMITTER: Vila-Farres X

PROVIDER: S-EPMC5666006 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Combating virulence of Gram-negative bacilli by OmpA inhibition.

Vila-Farrés Xavier X Parra-Millán Raquel R Sánchez-Encinales Viviana V Varese Monica M Ayerbe-Algaba Rafael R Bayó Nuria N Guardiola Salvador S Pachón-Ibáñez María Eugenia ME Kotev Martin M García Jesús J Teixidó Meritxell M Vila Jordi J Pachón Jerónimo J Giralt Ernest E Smani Younes Y

Scientific reports 20171031 1

Preventing the adhesion of pathogens to host cells provides an innovative approach to tackling multidrug-resistant bacteria. In this regard, the identification of outer membrane protein A (OmpA) as a key bacterial virulence factor has been a major breakthrough. The use of virtual screening helped us to identify a cyclic hexapeptide AOA-2 that inhibits the adhesion of Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli to host cells and the formation of biofilm, thereby preventin ...[more]

PMID: 29089624

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Project description:IntroductionCarbapenem-resistant gram-negative bacilli are a worldwide concern because of high morbidity and mortality rates. Additionally, the increasing prevalence of these bacteria is dangerous. To investigate the extent of antimicrobial resistance and prioritize the utility of novel drugs, we evaluated the molecular characteristics and antimicrobial susceptibility profiles of carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii in Ecuador in 2022.MethodsNinety-five clinical isolates of carbapenem non-susceptible gram-negative bacilli were collected from six hospitals in Ecuador. Carbapenem resistance was confirmed with meropenem disk diffusion assays following Clinical Laboratory Standard Institute guidelines. Carbapenemase production was tested using a modified carbapenemase inactivation method. Antimicrobial susceptibility was tested with a disk diffusion assay, the Vitek 2 System, and gradient diffusion strips. Broth microdilution assays were used to assess colistin susceptibility. All the isolates were screened for the blaKPC, blaNDM, blaOXA-48, blaVIM and blaIMP genes. In addition, A. baumannii isolates were screened for the blaOXA-23, blaOXA-58 and blaOXA-24/40 genes.ResultsCarbapenemase production was observed in 96.84% of the isolates. The blaKPC, blaNDM and blaOXA-48 genes were detected in Enterobacterales, with blaKPC being predominant. The blaVIM gene was detected in P. aeruginosa, and blaOXA-24/40 predominated in A. baumannii. Most of the isolates showed co-resistance to aminoglycosides, fluoroquinolones, and trimethoprim/sulfamethoxazole. Both ceftazidime/avibactam and meropenem/vaborbactam were active against carbapenem-resistant gram-negative bacilli that produce serin-carbapenemases.ConclusionThe epidemiology of carbapenem resistance in Ecuador is dominated by carbapenemase-producing K. pneumoniae harbouring blaKPC. Extensively drug resistant (XDR) P. aeruginosa and A. baumannii were identified, and their identification revealed the urgent need to implement strategies to reduce the dissemination of these strains.

Project description:IntroductionVentilator-associated pneumonias (VAPs) are a complication of mechanical ventilation in the intensive care unit (ICU) that increase length of stay, morbidity, and mortality. While identifying and treating infections early is paramount to improving patient outcomes, more and more data demonstrate limited courses of antibiotics improve outcomes. Prolonged (10-14 day) courses of antibiotics have remained the standard of care for pneumonia due to gram-negative bacilli (GNR). We aimed to review our GNR VAPs to assess risk factors for recurrent GNR infections.MethodsWe reviewed trauma patients who developed VAP from 02/2019 through 05/2022. Demographics, injury characteristics, and outcomes were reviewed with a focus on pneumonia details including the cultured pathogen(s), antibiotic(s) used, treatment duration, and presence of recurrent infections. We then compared single episode VAPs to multiple episode VAPs among patients infected by GNRs.ResultsEleven of the fifty trauma patients admitted to the ICU suffered a VAP caused by a GNR. Of these eleven patients, six experienced a recurrent infection, four of which were caused by Pseudomonas aeruginosa and two of which were caused by Enterobacter aerogenes. Among the patients who received ten days of antibiotic treatment, half suffered a recurrence. Although, there was no difference in the microbiology or antibiotic duration between the recurrences and single episodes.ConclusionDespite prolonged use of antibiotics, we found that the risk of recurrent or persistent infections was high among patients with VAP due to GNB. Further study is needed to determine optimal treatment to minimize the risk of these recurrences.Key messageVentilator-associated pneumonia due to gram-negative bacilli is a rare but high morbidity complication in intensive care units. Despite prolonged duration of therapy, these infections still appear to account for many recurrent infections and further study into optimal therapy is warranted.

Dataset Information

Combating virulence of Gram-negative bacilli by OmpA inhibition.

Publications

Combating virulence of Gram-negative bacilli by OmpA inhibition.

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