Developing new therapeutic approaches for treating infections caused by multi-drug resistant Acinetobacter baumannii

Gallagher, Peter; Baker, Stephen

doi:10.1016/j.jinf.2020.10.016

Cited by 34 publications

(19 citation statements)

References 52 publications

(56 reference statements)

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“…A. baumannii and S. aureus are some of the more common opportunistic pathogens which cause community and nosocomial infections. Unfortunately, the number of multidrug-resistant A. baumannii isolates has increased significantly [ 18 , 19 ]. Resistance to antibiotics is widespread in S. aureus , which methicillin-resistant S. aureus (MRSA) are the most important clinically [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial resistance among GLASS pathogens in Morocco: an epidemiological scoping review

et al. 2022

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Background Monitoring of antimicrobial resistance (AMR) is of great importance due to the frequency of strains becoming increasingly resistant to antibiotics. This review, using a public health focused approach, which aims to understand and describe the current status of AMR in Morocco in relation to WHO priority pathogens and treatment guidelines. Methods PubMed, ScienceDirect and Google Scholar Databases and grey literature are searched published articles on antimicrobial drug resistance data for GLASS priority pathogens isolated from Morocco between January 2011 and December 2021. Articles are screened using strict inclusion/exclusion criteria. AMR data is extracted with medians and IQR of resistance rates. Results Forty-nine articles are included in the final analysis. The most reported bacterium is Escherichia coli with median resistance rates of 90.9%, 64.0%, and 56.0%, for amoxicillin, amoxicillin-clavulanic acid, and co-trimoxazole, respectively. Colistin had the lowest median resistance with 0.1%. A median resistance of 63.0% is calculated for amoxicillin-clavulanic acid in Klebsiella pneumonia. Imipenem resistance with a median of 74.5% is reported for Acinetobacter baumannii. AMR data for Streptococcus pneumonie does not exceed 50.0% as a median. Conclusions Whilst resistance rates are high for most of GLASS pathogens, there are deficient data to draw vigorous conclusions about the current status AMR in Morocco. The recently join to the GLASS system surveillance will begin to address this data gap.

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Section: Introductionmentioning

confidence: 99%

Antimicrobial resistance among GLASS pathogens in Morocco: an epidemiological scoping review

et al. 2022

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“…Extensive and pan antibiotic-resistant A. baumannii infections are not only associated with poorer patient outcomes with significant morbidity and mortality but are also difficult to eradicate from clinical environments despite infection control procedures 2 . The success of the species as a serious global pathogen can be attributed to a highly plastic genome with significant mutation rates and frequent acquisition of genes that confer extensive antimicrobial resistance, increase virulence in the host, and/or enhance survival in unfavorable conditions over long periods 3 , 4 . These characteristics have favored the expansion of multi-drug resistant clonal lineages, including the two globally disseminated clones, global clone 1 (GC1) and global clone 2 (GC2), emphasizing a need to better understand mechanisms for virulence and survival in host and nosocomial contexts.…”

Section: Introductionmentioning

confidence: 99%

The Wzi outer membrane protein mediates assembly of a tight capsular polysaccharide layer on the Acinetobacter baumannii cell surface

Tickner

Hawas

Totsika

et al. 2021

Sci Rep

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Identification of novel therapeutic targets is required for developing alternate strategies to treat infections caused by the extensively drug-resistant bacterial pathogen, Acinetobacter baumannii. As capsular polysaccharide (CPS) is a prime virulence determinant required for evasion of host immune defenses, understanding the pathways for synthesis and assembly of this discrete cell-surface barrier is important. In this study, we assess cell-bound and cell-free CPS material from A. baumannii AB5075 wildtype and transposon library mutants and demonstrate that the Wzi outer membrane protein is required for the proper assembly of the CPS layer on the cell surface. Loss of Wzi resulted in an estimated 4.4-fold reduction in cell-associated CPS with a reciprocal increase in CPS material shed in the extracellular surrounds. Transmission electron microscopy revealed a disrupted CPS layer with sparse patches of CPS on the external face of the outer membrane when Wzi function was lost. However, this genotype did not have a significant effect on biofilm formation. Genetic analysis demonstrated that the wzi gene is ubiquitous in the species, though the nucleotide sequences were surprisingly diverse. Though divergence was not concomitant with variation at the CPS biosynthesis K locus, an association between wzi type and the first sugar of the CPS representing the base of the structure most likely to interact with Wzi was observed.

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“…Multidrug-or even pandrug-resistant Ac. baumannii are emerging pathogens associated with a range of infections and there is a pressing need to nd new therapeutics [42,43]. It should therefore be further explored whether saposin-like bacteriocins could be used alone or in combination with other antimicrobials to ght Ac.…”

Section: Discussionmentioning

confidence: 99%

Design of Novel Saposin-like Bacteriocins Using a Hybrid Approach

Oftedal,

Diep,

Kjos

2024

Preprint

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A multitude of approaches will be required to respond to the threat posed by the emergence and spread of antibiotic resistant pathogens. Bacteriocins have gained increasing attention as a possible alternative to antibiotics, as such peptide antimicrobials have mechanisms of action different from antibiotics and are therefore equally potent against antibiotic resistant bacteria as their susceptible counterparts. A group of bacteriocins known as saposin-like bacteriocins are believed to act directly on the bacterial membrane. Based on seven saposin-like leaderless bacteriocins, we have constructed a library of hybrid peptides containing all combinations of the N- and C-terminal halves of the native bacteriocins. All hybrid peptides were synthesized using in vitro protein expression and assayed for antimicrobial activity towards several pathogens. Of the 42 hybrid peptides, antimicrobial activity was confirmed for 11 novel hybrid peptides. Furthermore, several of the hybrid peptides exhibited altered antimicrobial spectra and apparent increase in potency compared to the peptides from which they were derived. The most promising hybrid, termed ISP26, was then obtained synthetically and shown to inhibit most of the Gram-positive species tested, including opportunistic pathogens and food spoilage bacteria. Additionally, ISP26 was shown to inhibit Acinetobacter, a species of Gram-negative bacteria frequently isolated from nosocomial infections. The activity of the hybrid library provides valuable insights into the design and screening of new active bacteriocins.

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Developing new therapeutic approaches for treating infections caused by multi-drug resistant Acinetobacter baumannii

Cited by 34 publications

References 52 publications

Antimicrobial resistance among GLASS pathogens in Morocco: an epidemiological scoping review

Antimicrobial resistance among GLASS pathogens in Morocco: an epidemiological scoping review

The Wzi outer membrane protein mediates assembly of a tight capsular polysaccharide layer on the Acinetobacter baumannii cell surface

Design of Novel Saposin-like Bacteriocins Using a Hybrid Approach

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