Dataset Information

Effects of synthetic peptide RP557 and its origin, LL-37, on carbapenem-resistant Pseudomonas aeruginosa.

ABSTRACT: Pseudomonas aeruginosa is a common bacterium in nosocomial infection. The biofilm-forming ability and antimicrobial resistance make P. aeruginosa biofilm infection refractory to patients requiring hospitalization, especially patients in the intensive care unit. Therefore, many alternative compounds have been developed. A newly synthesized peptide, RP557, derived from human cathelicidin LL-37, was evaluated for its antimicrobial and antibiofilm effect toward carbapenem-resistant P. aeruginosa (CRPA). The results showed that regardless of the resistance to carbapenems, the minimal inhibition concentrations of RP557 and LL-37 against P. aeruginosa were 32 µg/mL and 256 µg/mL, respectively. Both RP557 and LL-37 significantly reduced the P. aeruginosa biofilm mass at subMICs, while subMICs of carbapenems induced biofilm formation. RP557 could also remove approximately 50% of the mature biofilm at a concentration of 64 µg/mL, while 256 µg/mL LL-37 was needed to remove it. A quarter MIC of RP557 and LL-37 was used together with carbapenems (ertapenem, imipenem, and meropenem). The results show that both RP-557 and LL-37 might increase the susceptibility to CRPA by 4-16 times. Significant gene expression level changes were observed in RP557- or LL-37-treated CRPA. Confocal images showed that biofilm structures and biofilm cell viability were significantly reduced in the LL-37- or RP557-treated groups. Therefore, RP557 and its structural origin, LL-37, could be potential treatments for carbapenem-resistant P. aeruginosa infection, especially for chronic biofilm infection. IMPORTANCE Pseudomonas aeruginosa is one of the major pathogens of nosocomial infection. Combined its biofilm-forming ability with carbapenem-resistance, it is hard to handle P. aeruginosa infection, especially for patients requiring hospitalization. Antimicrobial peptide is a type of potential compound for bacterial infection treatment. Among these, RP557 was found effective in inhibiting biofilm previously. By assessing its effect on both carbapenem-resistant P. aeruginosa planktonic cells and biofilm, our results offered a potential treatment for carbapenem-resistant P. aeruginosa infection. It could be helpful to treat severe nosocomial infection related to carbapenem-resistant bacteria and increase the patients' survival rate.

SUBMITTER: Song YQ

PROVIDER: S-EPMC10581083 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Effects of synthetic peptide RP557 and its origin, LL-37, on carbapenem-resistant Pseudomonas aeruginosa.

Song Yun-Qi YQ Kyung Su Min SM Kim Suji S Kim Gun G Lee So Yeong SY Yoo Han Sang HS

Microbiology spectrum 20230809

Pseudomonas aeruginosa is a common bacterium in nosocomial infection. The biofilm-forming ability and antimicrobial resistance make P. aeruginosa biofilm infection refractory to patients requiring hospitalization, especially patients in the intensive care unit. Therefore, many alternative compounds have been developed. A newly synthesized peptide, RP557, derived from human cathelicidin LL-37, was evaluated for its antimicrobial and antibiofilm effect toward carbapenem-resistant ...[more]

PMID: 37555659

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Project description:Background:Colistin is a polypeptide antibiotic drug that targets lipopolysaccharides in the outer membrane of Gram-negative bacteria. Inactivation of the mgrB-gene is a common mechanism behind colistin-resistance in Klebsiella pneumoniae (Kpn). Since colistin is a cyclic polypeptide, it may exhibit cross-resistance with the antimicrobial peptide LL-37, and with other innate effector mechanisms, but previous results are inconclusive. Objective:To study potential cross-resistance between colistin and LL-37, as well as with other innate effector mechanisms, and to compare virulence of colistin-resistant and susceptible Kpn strains. Materials/Methods:Carbapenemase-producing Kpn from Oman (n = 17) were subjected to antimicrobial susceptibility testing and whole genome sequencing. Susceptibility to colistin and LL-37 was studied. The surface charge was determined by zeta-potential measurements and the morphology of treated bacteria was analyzed with electron microscopy. Bacterial survival was assessed in human whole blood and serum, as well as in a zebrafish infection-model. Results:Genome-analysis revealed insertion-sequences in the mgrB gene, as a cause of colistin resistance in 8/17 isolates. Colistin-resistant (Col-R) isolates were found to be more resistant to LL-37 compared to colistin-susceptible (Col-S) isolates, but only at concentrations ?50 ?g/ml. There was no significant difference in surface charge between the isolates. The morphological changes were similar in both Col-R and Col-S isolates after exposure to LL-37. Finally, no survival difference between the Col-R and Col-S isolates was observed in whole blood or serum, or in zebrafish embryos. Conclusion:Cross-resistance between colistin and LL-37 was observed at elevated concentrations of LL-37. However, Col-R and Col-S isolates exhibited similar survival in serum and whole blood, and in a zebrafish infection-model, suggesting that cross-resistance most likely play a limited role during physiological conditions. However, it cannot be ruled out that the observed cross-resistance could be relevant in conditions where LL-37 levels reach high concentrations, such as during infection or inflammation.

Project description:BackgroundCarbapenem-resistant Pseudomonas aeruginosa (CRPA) are a serious cause of healthcare-associated infections. Part of the infection prevention and control measures are outbreak investigations (OI) of patients, healthcare workers (HCW), and the environment after identifying a CRPA in order to identify carriers and environmental reservoirs, so that targeted actions can be taken to prevent further transmission. However, little is known on when and how to perform such OI. Therefore, this systematic review aims to summarize OI performed after detection of CRPA in the endemic and epidemic hospital setting.Main textArticles related to our research question were identified through a literature research in multiple databases (Embase, Medline Ovid, Cochrane, Scopus, Cinahl, Web of Science, and Google Scholar) until January 12, 2022 (Prospero registration number CRD42020194165). Hundred-twenty-six studies were included. In both the endemic and the epidemic setting, a median number of two out of seven predefined components of OI were identified. In the endemic setting, the most frequent component of OI was screening of the environment (28 studies, 62.2%). In the epidemic setting, screening of the environment (72 studies, 88.9%), and screening of patients during hospitalization (30 studies, 37%) were most frequently performed. Only 19 out of 126 studies (15.1%) reported screening of contact patients, and 37 studies reported screening of healthcare workers (HCW, 29.4%).ConclusionDue to probable underreporting of OI in the literature, the available evidence for the usefulness of the individual components of OI is scarce. This could lead to inhomogeneous performance of OI after detection of CRPA in the healthcare setting, and with this, potential under- or overscreening. While we could show evidence for the usefulness for environmental screening in order to identify the mode of transmission, evidence for HCW screening is scarce and might not lead to the identification of modes of transmission. Further studies are needed to better understand CI in different settings and, finally, develop guidance on when and how to best perform OI.

Dataset Information

Effects of synthetic peptide RP557 and its origin, LL-37, on carbapenem-resistant Pseudomonas aeruginosa.

Publications

Effects of synthetic peptide RP557 and its origin, LL-37, on carbapenem-resistant <i>Pseudomonas aeruginosa</i>.

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