Assessment of antivirulence activity of several d-amino acids against<i>Acinetobacter baumannii</i>and<i>Pseudomonas aeruginosa</i>

Rumbo, Carlos; Vallejo, Juán A.; Cabral, María P.; Martínez-Guitián, Marta; Pérez, Astrid; Beceiro, Alejandro; Bou, Germán

doi:10.1093/jac/dkw342

Cited by 26 publications

(28 citation statements)

References 38 publications

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“…Bacterial biofilms have significant impacts in industrial and clinical settings and there is therefore an urgent need to develop new compounds to prevent biofilm formation. Our data with AOA-2 showed remarkable results and are consistent with those previously reports for other inhibitors 29 , 32 , 33 .…”

Section: Resultssupporting

confidence: 93%

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Combating virulence of Gram-negative bacilli by OmpA inhibition

Vila-Farrés

Parra-Millán

Sánchez-Encinales

et al. 2017

Sci Rep

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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.

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Section: Resultssupporting

confidence: 93%

“…2D,E ). In the same line, other approach using D-amino acids has been performed recently to assess their antivirulence activity against A. baumannii and P. aeruginosa 29 , and showed that some of them can inhibit both pathogens adherence to eukaryotic cells and protect against infection of these eukaryotic cells with P. aeruginosa 29 .…”

Section: Resultsmentioning

confidence: 99%

Combating virulence of Gram-negative bacilli by OmpA inhibition

Vila-Farrés

Parra-Millán

Sánchez-Encinales

et al. 2017

Sci Rep

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“…The environmental factors, specifically the availability of certain amino acids, are reported as the anti‐biofilm properties in species such as Staphylococcus aureus , Bacillus subtilis and P. aeruginosa (Kolodkin‐Gal et al , ; Hochbaum et al , ; Leiman et al , ; Sanchez et al , ). Incubation of alveolar cells infected by P. aeruginosa with d ‐Cys, d ‐Trp and d ‐Arg reduced cell death (Rumbo et al , ). In addition, l ‐Arg significantly reduced bacterial spread and sepsis and increased animal survival in burned mice infected with P. aeruginosa (Everett et al , ).…”

Section: Discussionmentioning

confidence: 99%

Molecular insights into the master regulator CysB‐mediated bacterial virulence in Pseudomonas aeruginosa

Song

Yang

Chen

et al. 2019

Molecular Microbiology

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Pseudomonas aeruginosa is a major pathogen that causes serious acute and chronic infections in humans. The type III secretion system (T3SS) is an important virulence factor that plays essential roles in acute infections. However, the regulatory mechanisms of T3SS are not fully understood. In this study, we found that the deletion of cysB reduced the T3SS gene expression and swarming motility but enhanced biofilm formation. In a mouse acute pneumonia model, mutation of cysB decreased the average bacterial load compared to that of the wild-type strain. Further experiments demonstrated that CysB contributed to the reduced T3SS gene expression and bacterial pathogenesis by directly regulating the sensor kinase RetS. We also performed crystallographic studies of PaCysB. The overall fold of PaCysB NTD domain is similar to other LysR superfamily proteins and structural superposition revealed one possible DNA-binding model for PaCysB. Structural comparison also revealed great flexibility of the PaCysB RD domain, which may play an important role in bending and transcriptional regulation of target DNA. Taken together, these results expand our current understanding of the complex regulatory networks of T3SS and RetS pathways. The crystal structure of CysB provides new insights for studying the function of its homologs in other bacterial species.These authors contributed equally to this work.

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“…Several studies have shown that gallium nitrate or gallium protoporphyrin IX could be a viable therapeutic option for treating MDR A. baumannii (Antunes et al, 2012; Arivett et al, 2015). Some d -amino acids, such as d -His and d -Cys, inhibit bacterial growth, biofilm formation, and adherence to eukaryotic cells in A. baumannii (Rumbo et al, 2016). …”

Section: Prospective Treatment Optionsmentioning

confidence: 99%

Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

Lee

Park

et al. 2017

Front. Cell. Infect. Microbiol.

654

551

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Acinetobacter baumannii is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant A. baumannii, few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of A. baumannii is important. In this review, we summarize current studies on the virulence factors that contribute to A. baumannii pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of β-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant A. baumannii are summarized.

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Assessment of antivirulence activity of several d-amino acids againstAcinetobacter baumanniiandPseudomonas aeruginosa

Cited by 26 publications

References 38 publications

Combating virulence of Gram-negative bacilli by OmpA inhibition

Combating virulence of Gram-negative bacilli by OmpA inhibition

Molecular insights into the master regulator CysB‐mediated bacterial virulence in Pseudomonas aeruginosa

Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

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