Bacteriophage and Bacterial Susceptibility, Resistance, and Tolerance to Antibiotics

Abstract

Bacteriophages, viruses that infect and replicate within bacteria, impact bacterial responses to antibiotics in complex ways. Recent studies using lytic bacteriophages to treat bacterial infections (phage therapy) demonstrate that phages can promote susceptibility to chemical antibiotics and that phage/antibiotic synergy is possible. However, both lytic and lysogenic bacteriophages can contribute to antimicrobial resistance. In particular, some phages mediate the horizontal transfer of antibiotic resistance genes between bacteria via transduction and other mechanisms. In addition, chronic infection filamentous phages can promote antimicrobial tolerance, the ability of bacteria to persist in the face of antibiotics. In particular, filamentous phages serve as structural elements in bacterial biofilms and prevent the penetration of antibiotics. Over time, these contributions to antibiotic tolerance favor the selection of resistance clones. Here, we review recent insights into bacteriophage contributions to antibiotic susceptibility, resistance, and tolerance. We discuss the mechanisms involved in these effects and address their impact on bacterial fitness.

Bacteriophage Therapy of Multidrug-resistant Achromobacter in an 11-Year-old Boy With Cystic Fibrosis Assessed by Metagenome Analysis

“…26 However, after phage exposure, increased antibiotic susceptibility did occur in our patient, as previously reported in other cases, allowing combination therapy with phages and antibiotics to potentially be more effective than treatment with either alone. [27][28][29][30] Fortunately, no host neutralizing antibody response was detected to either Axy10 or JWX treatment phages in our patient, allowing for their potential use for retreatment if needed, assuming subsequent Achromobacter isolates remain susceptible to these phages.…”

“…26 However, after phage exposure, increased antibiotic susceptibility did occur in our patient, as previously reported in other cases, allowing combination therapy with phages and antibiotics to potentially be more effective than treatment with either alone. 27–30…”

Characterization and comprehensive genome analysis of novel bacteriophage, vB_Kpn_ZCKp20p, with lytic and anti-biofilm potential against clinical multidrug-resistant Klebsiella pneumoniae

“…Antimicrobial resistance is a versatile phenotype, contributed by several genetic mechanisms, including two major sets of mechanisms: acquisition of resistance genes, often horizontally, or mutation in conserved genes. So, we suggest that it is possible that plasmid- or integron-acquired resistance has endowed these bacterial strains with phage resistance as well, but this hypothesis remains to be tested ( Ojala et al., 2013 ; Chen et al., 2022 ).…”

Quantitative prediction of disinfectant tolerance inListeria monocytogenesusing whole genome sequencing and machine learning

“…Another two features returned hits for phage-related proteins. Phages are known to play a role in the horizontal transfer of genes, such as antimicrobial resistance genes [45]. One feature resulted in a hit for an LPXTG-domain-containing protein, which is a part of cell wall anchors but has no known link to disinfectant tolerance thus far.…”