PLoS Pathog 17(3):Įditor: Andreas Peschel, University of Tubingen, GERMANY (2021) Staphylococcus aureus cell wall structure and dynamics during host-pathogen interaction. Our study reveals an important adaptation to the host environment and the role of those components involved in cell wall homeostasis in vivo.Ĭitation: Sutton JAF, Carnell OT, Lafage L, Gray J, Biboy J, Gibson JF, et al. Conversely the peptidoglycan hydrolase SagB, whose loss results in thinner cell walls was attenuated in the murine systemic model of infection, with concomitant loss of fitness within macrophages. We tested the role of PBP4, known to increase cell wall crosslinking and found a pbp4 mutant to have increased survival in macrophages and fitness within the murine host. These features suggested the role of components controlling cell wall homeostasis as being important for infections.
Their cell wall peptidoglycan also is less crosslinked. aureus, isolated from an infected kidney abscess are smaller in size, with thicker cell walls than exponentially growing cells in vitro. aureus from the infected host to be able to analyse cellular morphology and structure. This is often hampered by the ability to obtain sufficient ex vivo pathogen samples for study. To discover new control regimes, it is therefore important to understand how the pathogen behaves within the relevant environment of the host. The prevalence of methicillin resistant Staphylococcus aureus (MRSA) in both hospitals and the wider community places a huge weight on healthcare providers. Our results, demonstrate the importance of appropriate cell wall structure and dynamics during pathogenesis, providing new insight to the mechanisms of disease. A combination of pbp4 and sagB deficiencies resulted in a restoration of parental virulence. However, loss of the other three enzymes Atl, SagA and ScaH resulted in clustering dependent attenuation, in a zebrafish embryo, but not a murine, model of infection. Loss of the major enzyme SagB, led to attenuation during murine infection and reduced survival in human macrophages. aureus has a family of 4 putative glucosaminidases, that are collectively crucial for growth. Thicker cell walls correlate with reduced activity of peptidoglycan hydrolases.
aureus from the livers of infected mice, which coincided with enhanced fitness within murine and human macrophages. Loss of PBP4 resulted in an increased recovery of S. aureus missing penicillin binding protein 4 (PBP4) has reduced peptidoglycan crosslinking in vitro its role during infection was established. These features suggested a role for specific peptidoglycan homeostatic mechanisms in disease. Isolated ex vivo bacterial cells are smaller than those actively growing in vitro, with thickened cell walls and reduced peptidoglycan crosslinking, similar to that of stationary phase cells. In this study we have developed methods to harvest bacteria from an active infection in order to purify cell walls for biochemical analysis ex vivo. Despite this importance, and the wealth of data from in vitro studies, we do not understand the structure and dynamics of peptidoglycan during infection. Peptidoglycan is the major structural component of the Staphylococcus aureus cell wall, in which it maintains cellular integrity, is the interface with the host, and its synthesis is targeted by some of the most crucial antibiotics developed.
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