Characterization of Pseudomonas aeruginosa
            <scp>l,d</scp>
            -Transpeptidases and Evaluation of Their Role in Peptidoglycan Adaptation to Biofilm Growth

The bacterial cell wall, a sophisticated and dynamic structure predominantly composed of peptidoglycan (PG), plays a pivotal role in bacterial survival and adaptation. Bacteria actively modify their cell walls by editing PG components in response to environmental challenges. Diverse variations in peptide composition, cross-linking patterns, and glycan strand structures empower bacteria to resist antibiotics, evade host immune detection, and adapt to dynamic environments. This review comprehensively summarizes the most common modifications reported to date and their associated adaptive role and further highlights how regulation of PG synthesis and turnover provides resilience to cell lysis.

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In vivo evolution of antimicrobial resistance in a biofilm model of Pseudomonas aeruginosa lung infection

Higazy,

Pham,

van Hasselt

et al. 2024

The ISME Journal

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The evolution of antimicrobial resistance (AMR) in biofilms has been repeatedly studied by experimental evolution in vitro, but rarely in vivo. The complex microenvironment at the infection site imposes selective pressures on the bacterial biofilms, potentially influencing the development of AMR. We report here the development of AMR in an in vivo mouse model of Pseudomonas aeruginosa biofilm lung infection. P. aeruginosa embedded in seaweed alginate beads underwent four successive lung infection passages with or without ciprofloxacin exposure (CIP). The development of CIP resistance was assessed at each passage by population analysis of the bacterial populations recovered from the lungs of CIP-treated and control mice, with subsequent whole genome sequencing of selected isolates. As inflammation plays a crucial role in shaping the microenvironment at the infection site, its impact was explored through the measurement of cytokine levels in the lung homogenate. A rapid development of AMR was observed starting from the second passage in the CIP-treated mice. Genetic analysis revealed mutations in nfxB, efflux pumps (mexZ), and two-component systems (parS) contribution to CIP resistance. The control group isolates exhibited mutations in the dipA gene, likely associated with biofilm dispersion. In the initial two passages, the CIP-treated group exhibited an elevated inflammatory response compared to the control group. This increase may potentially contribute to the release of mutagenic reactive oxygen species and the development of AMR. In conclusion, this study illustrates the complex relationship between infection, antibiotic treatment, and immune response.

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Characterization of Pseudomonas aeruginosa l,d -Transpeptidases and Evaluation of Their Role in Peptidoglycan Adaptation to Biofilm Growth

Cited by 3 publications

References 59 publications

Bacterial peptidoglycan as a living polymer

Bacterial peptidoglycan as a living polymer

Mechanisms conferring bacterial cell wall variability and adaptivity

In vivo evolution of antimicrobial resistance in a biofilm model of Pseudomonas aeruginosa lung infection

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