Regulation of virulence and antibiotic resistance in Gram-positive microbes in response to cell wall-active antibiotics

Abstract

Purpose of review: Antibiotic stress can evoke considerable genotypic and phenotypic changes in Gram-positive bacteria. Here, we review recent studies describing altered virulence expression in response to cell wall-acting antibiotics and discuss mechanisms that coordinate regulation of the antibiotic response. Recent findings: Pleiotropic effects induced by antibiotic exposure include alterations to bacterial metabolism, cell wall structure and antibiotic resistance. In addition, subinhibitory concentrations of cell wall-active antibiotics have increasingly been shown to induce the production of exotoxins and biofilm formation that may influence virulence. Remarkably, phenotypes associated with comparable antibiotic stresses can vary considerably, emphasizing the need to better understand the response to cell wall-active antibiotics. Recent studies support both direct antibiotic recognition and recognition of antibiotic-induced stress to the bacterial cell wall. Specifically, bacterial two-component systems, PASTA kinases and conserved oxidative-stress sensors each contribute to modulating the antibiotic stress response. Summary: Bacterial sensory systems and global regulators coordinate signaling in response to cell wall-active antibiotics. Regulation of the antibiotic response is complex and involves integration of signals from multiple response pathways. A better definition of the antibiotic stress response among Gram-positive pathogens may yield novel therapeutic targets to counter antibiotic resistance and virulence factor expression.

Biofilms: Novel Strategies Based on Antimicrobial Peptides

“…Instead, the majority of the bacteria are organized in more complex structures known as biofilms. Accordingly, more than 80% of all bacterial infections are due to microorganisms in their biofilm mode of growth [1].…”

β-Lactams against the Fortress of the Gram-Positive Staphylococcus aureus Bacterium

“…The renewed interest in structure–activity development of the nucleoside-mimetic natural product inhibitors of MraY ,− and the recognition that numerous antibiotics interfere with peptidoglycan biosynthesis by complexation with the undecaprenol diphosphate (in both Gram-positive ,− and Gram-negative bacteria , ) and/or Lipid II ,,,− ) are notable recent developments. Indeed, the recognition of the fastidiousness of the intertwined biosynthetic cycles for Lipid II synthesis, , for Lipid II assembly into the peptidoglycan, and for peptidoglycan recycling (with preeminent natural product antibacterials targeting within each cycle) − have led to substantial effort toward answering whether concurrent inhibition of two of these cycles (and their regulatory systems) achieves meaningful antibiotic synergism.…”

Proteomic Characterization of Antibiotic Resistance, and Production of Antimicrobial and Virulence Factors in Streptococcus Species Associated with Bovine Mastitis. Could Enzybiotics Represent Novel Therapeutic Agents Against These Pathogens?

“…ST3 strains also contained an additional peptide, corresponding to a protein involved in the microbial response to antibiotics, which attacks the bacterial cell wall. This protein recognizes perturbations in the cell envelope, caused by antibiotics such as bacitracin and vancomycin, which interfere with the lipid II metabolism and the undecaprenyl cycle [30]. Another peptide, also identified in the ST3 strain, corresponds to a streptomycin adenylyltransferase, a protein that mediates bacterial resistance to the antibiotics streptomycin and spectinomycin [31].…”