Genomic Insights into the Distribution and Phylogeny of Glycopeptide Resistance Determinants within the Actinobacteria Phylum.

Andrés Andreo-Vidal,Elisa Binda,Oleksandr Yushchuk,Victor Fedorenko,Flavia Marinelli

doi:10.3390/antibiotics10121533

Andrés Andreo-Vidal, Elisa Binda + Show 3 more

Open Access

https://doi.org/10.3390/antibiotics10121533

Copy DOI

Journal: Antibiotics	Publication Date: Dec 14, 2021
Citations: 4	License type: CC BY 4.0

Affiliation: University of Insubria, Lviv University

Abstract

The spread of antimicrobial resistance (AMR) creates a challenge for global health security, rendering many previously successful classes of antibiotics useless. Unfortunately, this also includes glycopeptide antibiotics (GPAs), such as vancomycin and teicoplanin, which are currently being considered last-resort drugs. Emerging resistance towards GPAs risks limiting the clinical use of this class of antibiotics—our ultimate line of defense against multidrug-resistant (MDR) Gram-positive pathogens. But where does this resistance come from? It is widely recognized that the GPA resistance determinants—van genes—might have originated from GPA producers, such as soil-dwelling Gram-positive actinobacteria, that use them for self-protection. In the current work, we present a comprehensive bioinformatics study on the distribution and phylogeny of GPA resistance determinants within the Actinobacteria phylum. Interestingly, van-like genes (vlgs) were found distributed in different arrangements not only among GPA-producing actinobacteria but also in the non-producers: more than 10% of the screened actinobacterial genomes contained one or multiple vlgs, while less than 1% encoded for a biosynthetic gene cluster (BGC). By phylogenetic reconstructions, our results highlight the co-evolution of the different vlgs, indicating that the most diffused are the ones coding for putative VanY carboxypeptidases, which can be found alone in the genomes or associated with a vanS/R regulatory pair.

Highlights

Starting with the discovery of penicillin [1], humanity has been involved in a neverending arms race between life-threatening bacterial pathogens and antibiotics, either natural, semisynthetic or completely synthetic
Thanks to the abundance of genomic data on actinobacteria today, our aim is to prove or disprove the assumption that vlgs are peculiar to Glycopeptide antibiotics (GPAs) producers, and to clarify how these genes are eventually distributed and organized among different orders belonging to Actinobacteria phylum
We found that the two Type IV GPA producers—N. gerenzanensis

Summary

Introduction

Starting with the discovery of penicillin [1], humanity has been involved in a neverending arms race between life-threatening bacterial pathogens and antibiotics, either natural, semisynthetic or completely synthetic. Interagency Coordination Group on Antimicrobial Resistance in 2014 predicted that the spread of antimicrobial resistance (AMR) will cause up to 10 million deaths per year by. Recent events might make this number even more grim: the worldwide health crisis caused by SARS-CoV-2 has led to an increase in antibiotic use and misuse, which, in turn, is likely to further accelerate AMR diffusion [3]. AMR has rendered many previously successful groups of antibiotics non-functional, leaving us hiding behind the “thin red line” of last-resort drugs, capable to combat multidrug-resistant (MDR). Glycopeptide antibiotics (GPAs) are a class of non-ribosomally synthesized, highly cross-linked, halogenated and glycosylated natural products, which are considered frontline drugs against Gram-positive MDR pathogens such as Staphylococcus aureus, Enterococcus spp., Clostridioides difficile, etc. Glycopeptide antibiotics (GPAs) are a class of non-ribosomally synthesized, highly cross-linked, halogenated and glycosylated natural products, which are considered frontline drugs against Gram-positive MDR pathogens such as Staphylococcus aureus, Enterococcus spp., Clostridioides difficile, etc. [4].

Objectives

Results

Conclusion