TY - JOUR
T1 - Persistence of obligate intracellular pathogens
T2 - alternative strategies to overcome host-specific stresses
AU - Riffaud, Camille M.
AU - Rucks, Elizabeth A.
AU - Ouellette, Scot P.
N1 - Funding Information:
The authors are grateful to members of the Ouellette and Rucks labs for thoughtful discussions. We apologize to any authors whose work was not adequately discussed due to space constraints. This work was supported by a National Institutes of Health (NIAID) award to SO and ER (1R01AI132406) as well as a CAREER award from the National Science Foundation to SO (1810599.
Publisher Copyright:
Copyright © 2023 Riffaud, Rucks and Ouellette.
PY - 2023
Y1 - 2023
N2 - In adapting to the intracellular niche, obligate intracellular bacteria usually undergo a reduction of genome size by eliminating genes not needed for intracellular survival. These losses can include, for example, genes involved in nutrient anabolic pathways or in stress response. Living inside a host cell offers a stable environment where intracellular bacteria can limit their exposure to extracellular effectors of the immune system and modulate or outright inhibit intracellular defense mechanisms. However, highlighting an area of vulnerability, these pathogens are dependent on the host cell for nutrients and are very sensitive to conditions that limit nutrient availability. Persistence is a common response shared by evolutionarily divergent bacteria to survive adverse conditions like nutrient deprivation. Development of persistence usually compromises successful antibiotic therapy of bacterial infections and is associated with chronic infections and long-term sequelae for the patients. During persistence, obligate intracellular pathogens are viable but not growing inside their host cell. They can survive for a long period of time such that, when the inducing stress is removed, reactivation of their growth cycles resumes. Given their reduced coding capacity, intracellular bacteria have adapted different response mechanisms. This review gives an overview of the strategies used by the obligate intracellular bacteria, where known, which, unlike model organisms such as E. coli, often lack toxin-antitoxin systems and the stringent response that have been linked to a persister phenotype and amino acid starvation states, respectively.
AB - In adapting to the intracellular niche, obligate intracellular bacteria usually undergo a reduction of genome size by eliminating genes not needed for intracellular survival. These losses can include, for example, genes involved in nutrient anabolic pathways or in stress response. Living inside a host cell offers a stable environment where intracellular bacteria can limit their exposure to extracellular effectors of the immune system and modulate or outright inhibit intracellular defense mechanisms. However, highlighting an area of vulnerability, these pathogens are dependent on the host cell for nutrients and are very sensitive to conditions that limit nutrient availability. Persistence is a common response shared by evolutionarily divergent bacteria to survive adverse conditions like nutrient deprivation. Development of persistence usually compromises successful antibiotic therapy of bacterial infections and is associated with chronic infections and long-term sequelae for the patients. During persistence, obligate intracellular pathogens are viable but not growing inside their host cell. They can survive for a long period of time such that, when the inducing stress is removed, reactivation of their growth cycles resumes. Given their reduced coding capacity, intracellular bacteria have adapted different response mechanisms. This review gives an overview of the strategies used by the obligate intracellular bacteria, where known, which, unlike model organisms such as E. coli, often lack toxin-antitoxin systems and the stringent response that have been linked to a persister phenotype and amino acid starvation states, respectively.
KW - Chlamydia
KW - Coxiella
KW - interferon-gamma
KW - iron starvation
KW - obligate intracellular bacteria
KW - persistence
KW - stringent response
KW - tryptophan starvation
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U2 - 10.3389/fcimb.2023.1185571
DO - 10.3389/fcimb.2023.1185571
M3 - Review article
C2 - 37284502
AN - SCOPUS:85161029458
SN - 2235-2988
VL - 13
JO - Frontiers in Cellular and Infection Microbiology
JF - Frontiers in Cellular and Infection Microbiology
M1 - 1185571
ER -