Enhanced Efflux Activity Facilitates Drug Tolerance in Dormant Bacterial Cells

Pu, Yonglin; Zhao, Zhilun; Li, Yingxing; Zou, Jin; Ma, Qi; Zhao, Yanna; Ke, Yuehua; Zhu, Yun; Chen, Huiyi; Baker, Matthew A. B.; Ge, Hao; Sun, Yujie; Xie, X. Sunney; Bai, Fan

doi:10.1016/j.molcel.2016.03.035

Cited by 337 publications

(342 citation statements)

References 48 publications

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“…This is also very well established [e.g., Ref. (139, 190–203)]. In many cases, they can hide intracellularly (204), where antibiotics often penetrate poorly (205) because the necessary transporters (206–209) are absent.…”

Section: Prevalence Of Dormant Persistent or Latent Bacteria In Infmentioning

confidence: 79%

A Dormant Microbial Component in the Development of Preeclampsia

Kell

Kenny

2016

Front. Med.

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Preeclampsia (PE) is a complex, multisystem disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused. We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is, in fact, microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, and urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of “preeclampsia” that we assessed has, in fact, also been shown to be raised in response to infection. An infectious component to PE fulfills the Bradford Hill criteria for ascribing a disease to an environmental cause and suggests a number of treatments, some of which have, in fact, been shown to be successful. PE was classically referred to as endotoxemia or toxemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the etiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.

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Section: Prevalence Of Dormant Persistent or Latent Bacteria In Infmentioning

confidence: 79%

A Dormant Microbial Component in the Development of Preeclampsia

Kell

Kenny

2016

Front. Med.

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“…Antibiotic treatment and environmental stresses can give rise to population heterogeneity and confer phenotypic protection against lethality [81]; simple examples include variable expression of multi-drug efflux pumps [82] and stochastic formation of persister cells by toxin-antitoxin systems and the ppGpp-mediated stringent response [83,84]. Recent studies have revealed several additional persister mechanisms, including ATP depletion [85,86], morphological differentiation [87], inter-cell signaling [88,89], and toxin-antitoxin-mediated inhibition of proton-motive force [90,91] or protein translation [92].…”

Section: Environmental Factorsmentioning

confidence: 99%

Antibiotic efficacy — context matters

Yang

Bening

Collins

2017

Current Opinion in Microbiology

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Antibiotic lethality is a complex physiological process, sensitive to external cues. Recent advances using systems approaches have revealed how events downstream of primary target inhibition actively participate in antibiotic death processes. In particular, altered metabolism, translational stress and DNA damage each contribute to antibiotic-induced cell death. Moreover, environmental factors such as oxygen availability, extracellular metabolites, population heterogeneity and multidrug contexts alter antibiotic efficacy by impacting bacterial metabolism and stress responses. Here we review recent studies on antibiotic efficacy and highlight insights gained on the involvement of cellular respiration, redox stress and altered metabolism in antibiotic lethality. We discuss the complexity found in natural environments and highlight knowledge gaps in antibiotic lethality that may be addressed using systems approaches.

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“…La lenta eliminación de esta sub-población de bacterias persistentes puede ser explicada porque la actividad de CFX se redujo a causa de la disminuida respiración celular (Lobritz et al, 2015) y la mayor actividad de las bombas de eflujo de este tipo de bacterias (Pu et al, 2016). La presencia de una subpoblación de bacterias persistentes determinó que la erradicación de E. coli 09-684 pasara a depender del tiempo de exposición a CFX.…”

Section: Modo De Acción De Cfx Sobre E Coli 09-684unclassified

Actividad antibacteriana in vitro de Ciprofloxacina sobre una cepa autóctona de Escherichia coli: efecto del pH sobre su potencia y efecto de la persistencia bacteriana sobre su modo de acción

Patricelli¹,

Dell'elce²,

Weidmann³

et al. 2017

FAVE Cs Vet

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RESUMEN. En este trabajo se evaluó in vitro:(i) el efecto del pH sobre la actividad bactericida de ciprofloxacina (CFX) frente a una cepa autóctona de Escherichia coli y (ii) el efecto de las bacterias persistentes sobre el modo de acción concentración dependiente de CFX. La actividad antibacteriana de CFX disminuyó a causa del descenso del pH, por lo que los valores de concentración inhibitoria mínima (CIM), concentración bactericida mínima (CBM) y concentración de erradicación bacteriana mínima (CEBM) se incrementaron cuando el pH del medio de cultivo descendió de 7,4 a valores de 6,5 y 5,5. La cinética de eliminación bacteriana de CFX fue bifásica a causa de la selección de una sub-población de bacterias persistentes que presentaron una velocidad de eliminación más lenta. Por lo tanto la actividad bactericida de CFX fue definida por su concentración en relación a la CIM y el tiempo durante el cual se mantuvo la exposición de las bacterias a ésta.SUMMARY. In vitro antibacterial activity of ciprofloxacin against a native strain of Escherichia coli: effect of pH on its potency and effect of bacterial persistence on its mode of action. In this in vitro assay was evaluated: (i) the effect of pH on the bactericidal activity of ciprofloxacin (CFX) against a native strain of Escherichia coli, (ii) the effect of persister bacteria on the concentration-dependent mode of action of CFX. The antibacterial activity of CFX decreased with reductions of pH, so the values of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimum eradication bacterial concentration (MEBC) were increased when the pH of the culture medium decreased from 7.4 to 6.5 and 5.5. The kinetics of bacterial elimination of CFX presented a biphasic pattern because of the selection of a sub-population of persistent bacteria which presented a slower elimination rate. Therefore, the antibacterial activity of CFX was determined by its concentration in reference to MIC values and the time during which the exposure of the bacteria was maintained.Palabras clave: Escherichia coli, eficacia, modo de acción, pH, bacterias persistentes.

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Enhanced Efflux Activity Facilitates Drug Tolerance in Dormant Bacterial Cells

Cited by 337 publications

References 48 publications

A Dormant Microbial Component in the Development of Preeclampsia

A Dormant Microbial Component in the Development of Preeclampsia

Antibiotic efficacy — context matters

Actividad antibacteriana in vitro de Ciprofloxacina sobre una cepa autóctona de Escherichia coli: efecto del pH sobre su potencia y efecto de la persistencia bacteriana sobre su modo de acción

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