Acinetobacter baumannii Can Survive with an Outer Membrane Lacking Lipooligosaccharide Due to Structural Support from Elongasome Peptidoglycan Synthesis

Simpson, Brent W.; Nieckarz, Marta; Pinedo, Víctor; McLean, Amanda B.; Cava, Felipe; Trent, M Stephen

doi:10.1128/mbio.03099-21

Cited by 40 publications

(38 citation statements)

References 69 publications

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“…3h ), a gene of unknown function but predicted as an LPS O-antigen polymerase (Manning et al, 1995). This result is in agreement with recent reports pointing the cooperative crosstalk between PG and LPS to maintain envelope integrity (Boll et al, 2016; Goodall et al, 2021; Simpson et al, 2021).…”

Section: Resultssupporting

confidence: 94%

Genome-wide peptidoglycan profiling of Vibrio cholerae

Hernández

Álvarez

Ritzl-Rinkenberger

et al. 2022

Preprint

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Most bacteria cells are protected by a peptidoglycan cell wall. Defining the chemical structure of the peptidoglycan has been instrumental to characterize cell wall associated proteins and to illuminate the mode of action of cell wall-acting antibiotics. However, a major roadblock for a comprehensive understanding of peptidoglycan homeostasis has been the lack of methods to conduct large-scale, systematic studies. Here we have developed and applied an innovative high throughput peptidoglycan analytical pipeline to analyze the entire non-essential, arrayed mutant library of Vibrio cholerae. The unprecedented breadth of these analyses revealed that peptidoglycan homeostasis is preserved by a large percentage of the genome organized in complex networks that functionally link peptidoglycan features with genetic determinants. As an example, we discovered a novel bifunctional penicillin-binding protein in V. cholerae. Collectively, genome-wide peptidoglycan profiling provides a fast, easy, and unbiased method for systematic identification of the genetic determinants of peptidoglycan synthesis and remodeling.

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Section: Resultssupporting

confidence: 94%

Genome-wide peptidoglycan profiling of Vibrio cholerae

Hernández

Álvarez

Ritzl-Rinkenberger

et al. 2022

Preprint

Self Cite

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“…In A . baumannii , proteins that synthesize PG in lateral cell walls (the elongasome) are critical for the fitness of lipid A-deficient strains, suggesting that alterations in PG structure are needed to compensate for the OM’s loss of mechanical strength ( Simpson et al, 2021 ). Because elongasome components are essential for viability in Caulobacter ( Christen et al, 2011 ), RB-TnSeq could not reveal their fitness effects in CHIR-090-treated cultures.…”

Section: Discussionmentioning

confidence: 99%

Caulobacter lipid A is conditionally dispensable in the absence of fur and in the presence of anionic sphingolipids

et al. 2022

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“… 2020 ), whereas LOS/LPS prevents vancomycin uptake by Gram-negative bacteria (Simpson et al . 2021 ). Therefore, the Gram-negative cell envelope affects bacterial susceptibility to different classes of antibiotics.…”

Section: Introductionmentioning

confidence: 99%

Gram-negative bacteria act as a reservoir for aminoglycoside antibiotics that interact with host factors to enhance bacterial killing in a mouse model of pneumonia

et al. 2022

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In vitro exposure of multiple Gram-negative bacteria to an aminoglycoside (AG) antibiotic has previously been demonstrated to result in bacterial alterations that interact with host factors to suppress Gram-negative pneumonia. However, the mechanisms resulting in suppression are not known. Here, the hypothesis that Gram-negative bacteria bind and retain AGs, which are introduced into the lung and interact with host defenses to affect bacterial killing, was tested. Following in vitro exposure of one of several, pathogenic Gram-negative bacteria to the AG antibiotics kanamycin or gentamicin, AGs were detected in bacterial cell pellets (up to 208 μg/mL). Using inhibitors of AG binding and internalization, the bacterial outer membrane was implicated as the predominant kanamycin and gentamicin reservoir. Following intranasal administration of gentamicin-bound bacteria or gentamicin solution at the time of infection with live, AG-naïve bacteria, gentamicin was detected in the lungs of infected mice (up to 8 μg/g). Co-inoculation with gentamicin-bound bacteria resulted in killing of AG-naïve bacteria by up to 3-log10, mirroring the effects of intranasal gentamicin treatment. In vitro killing of AG-naïve bacteria mediated by kanamycin-bound bacteria required the presence of detergents or pulmonary surfactant, suggesting that increased bacterial killing inside the murine lung is facilitated by the detergent component of pulmonary surfactant. These findings demonstrate that Gram-negative bacteria bind and retain AGs that can interact with host-derived pulmonary surfactant to enhance bacterial killing in the lung. This may help explain why AGs appear to have unique efficacy in the lung and might expand their clinical utility.

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Acinetobacter baumannii Can Survive with an Outer Membrane Lacking Lipooligosaccharide Due to Structural Support from Elongasome Peptidoglycan Synthesis

Abstract: Gram-negative bacteria have a multilayered cell envelope with a layer of cross-linked polymers (peptidoglycan) sandwiched between two membranes. Peptidoglycan was long thought to exclusively provide rigidity to the cell providing mechanical strength.

Cited by 40 publications

References 69 publications

Genome-wide peptidoglycan profiling of Vibrio cholerae

Genome-wide peptidoglycan profiling of Vibrio cholerae

Caulobacter lipid A is conditionally dispensable in the absence of fur and in the presence of anionic sphingolipids

Gram-negative bacteria act as a reservoir for aminoglycoside antibiotics that interact with host factors to enhance bacterial killing in a mouse model of pneumonia

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