IntracellularStaphylococcus aureusand host cell death pathways

Abstract

Staphylococcus aureus is a major opportunistic human pathogen that is globally prevalent. Although S. aureus and humans may have co‐evolved to the point of commensalism, the bacterium is equipped with virulence factors causing devastating infections. The adoption of an intracellular lifestyle by S. aureus is an important facet of its pathogenesis. Occupying a privileged intracellular compartment permits evasion from the bactericidal actions of host immunity and antibiotics. However, this localization exposes S. aureus to cell‐intrinsic processes comprising autophagy, metabolic challenges and clearance mechanisms orchestrated by host programmed cell death pathways (PCDs), including apoptosis, pyroptosis and necroptosis. Mounting evidence suggests that S. aureus deploys pathoadaptive mechanisms that modulate the expression of its virulence factors to prevent elimination through PCD pathways. In this review, we critically analyse the current literature on the interplay between S. aureus virulence factors with the key, intertwined nodes of PCD. We discuss how S. aureus adaptation to the human host plays an essential role in the evasion of PCD, and we consider future directions to study S. aureus–PCD interactions.

Differential Early in vivo Dynamics and Functionality of Recruited Polymorphonuclear Neutrophils After Infection by Planktonic or Biofilm Staphylococcus aureus

“…These results were further corroborated by the semi-quantitative measure of EGFP + phagocyte recruitment in the ear pinna tissue, and observations of bacterial injection sites showing a considerable recruitment of leukocytes for both bacterial forms. S. aureus is known to produce toxins and enzymes, such as leukocidins and coagulase, that are able to induce cell death by apoptosis, necroptosis, and also pyroptosis ( Soe et al, 2021 ). This was coherent with ear pinna tissue necrosis observed as early as day 3.…”

Exploring the Role of Staphylococcus aureus in Inflammatory Diseases

“…S. aureus can activate NLRP3 and lead to MAC-T cell pyroptosis via the K + efflux pathway, and the homeostatic phenotype of resident macrophages can also orchestrate the early inflammatory response via the inflammasome pathway and subsequent pyroptosis [ 252 , 253 ]. It was found that the S. aureus associated-PAMPs, i.e., LTA [ 125 ], triacyl lipopetides [ 124 ], diacyl lipoproteins [ 151 ], and PGN [ 140 ], and S. aureus toxins, enzymes, and effectors, i.e., PVL [ 62 ],α-Hla [ 143 ], Hlb [ 34 ], and Hlg [ 35 ], can mediate pyroptosis [ 16 ].…”

“…PVL [ 63 ], Hla [ 43 ], and PSMs [ 69 ] induce the necroptosis of host cells after S. aureus infection [ 16 ]. In pneumonia and psoriasis, S. aureus infection induces necroptosis through RIP1/RIP3/MLKL signaling.…”

“…Bacterial pathogens increase their chances of survival by disrupting host programmed cell death (PCD). S. aureus is recognized by homologous host receptors, and the bacteria adhere and enter non-phagocytic cells, triggering programmed cellular necrosis through either intrinsic pathway mitochondrial damage or the extrinsic pathway in response to cell surface receptor engagement [ 16 , 63 , 255 , 256 ]. TNF and TLR3/TLR4 activation triggered necroptosis through a downstream signaling complex containing RIPK1, RIPK3, and MLKL.…”

“…S. aureus infection and toxins can activate a variety of inflammatory cells, such as keratinocytes [ 5 ], helper T cells [ 6 ], innate lymphoid cells (ILCs) [ 7 ], macrophages [ 8 ], dendritic cells (DCs) [ 9 ], mast cells [ 10 ], neutrophils [ 11 ], eosinophils [ 12 ], and basophils [ 13 ], which release inflammatory factors that accumulate at the site of infection and cause an inflammatory response. During infection, S. aureus can also induce host cell death through programmed forms of cell death, such as pyroptosis [ 14 ], apoptosis [ 15 ], necroptosis [ 16 ], and autophagy [ 17 ].…”