Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages

Miskinyte, Migla; Gordo, Isabel

doi:10.1128/aac.01632-12

Cited by 45 publications

(49 citation statements)

References 53 publications

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“…The relative fitness of susceptible and resistant bacteria is measured by their reproductive success during in vitro culture. Many studies have reported that resistance commonly creates a fitness burden (51, 52); however, resistant mutants with no measurable costs or those with a slight advantage over the wild type have also been observed (53,54), which is in agreement with our observations. However, in the presence of 10 g ml Ϫ1 CHX, the biomass of the WT15 biofilms increased over a 24-h period, whereas there was an apparent cessation of biofilm development in the CHX-treated MT51 biofilms compared to that in their untreated counterparts.…”

Section: Discussionsupporting

confidence: 83%

Microscopic and Spectroscopic Analyses of Chlorhexidine Tolerance in Delftia acidovorans Biofilms

Rema

Lawrence

Dynes

et al. 2014

Antimicrob Agents Chemother

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The physicochemical responses of Delftia acidovorans biofilms exposed to the commonly used antimicrobial chlorhexidine (CHX) were examined in this study. A CHX-sensitive mutant (MIC, 1.0 g ml ؊1 ) was derived from a CHX-tolerant (MIC, 15.0 g ml ؊1 ) D. acidovorans parent strain using transposon mutagenesis. D. acidovorans mutant (MT51) and wild-type (WT15) strain biofilms were cultivated in flow cells and then treated with CHX at sub-MIC and inhibitory concentrations and examined by confocal laser scanning microscopy (CLSM), scanning transmission X-ray microscopy (STXM), and infrared (IR) spectroscopy. Specific morphological, structural, and chemical compositional differences between the CHX-treated and -untreated biofilms of both strains were observed. Apart from architectural differences, CLSM revealed a negative effect of CHX on biofilm thickness in the CHX-sensitive MT51 biofilms relative to those of the WT15 strain. STXM analyses showed that the WT15 biofilms contained two morphochemical cell variants, whereas only one type was detected in the MT51 biofilms. The cells in the MT51 biofilms bioaccumulated CHX to a similar extent as one of the cell types found in the WT15 biofilms, whereas the other cell type in the WT15 biofilms did not bioaccumulate CHX. STXM and IR spectral analyses revealed that CHX-sensitive MT51 cells accumulated the highest levels of CHX. Pretreating biofilms with EDTA promoted the accumulation of CHX in all cells. Thus, it is suggested that a subpopulation of cells that do not accumulate CHX appear to be responsible for greater CHX resistance in D. acidovorans WT15 biofilm in conjunction with the possible involvement of bacterial membrane stability.

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Section: Discussionsupporting

confidence: 83%

Microscopic and Spectroscopic Analyses of Chlorhexidine Tolerance in Delftia acidovorans Biofilms

Rema

Lawrence

Dynes

et al. 2014

Antimicrob Agents Chemother

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“…Many of these pathogens persist inside the cells of the immune system. Miskinyte and Gordo (Miskinyte and Gordo 2013) examined how a commensal E. coli was able to develop the virulence needed to persist inside macrophages of the immune system. Working in mice, they found that when maintained in vitro under the selective pressure of host macrophages, commensal E. coli can evolve virulent clones that escape phagocytosis and macrophage killing in vitro , while increasing their pathogenicity in vivo .…”

Section: Commensal Bacteria At the Crossroad Between Inflammation Andmentioning

confidence: 99%

Maternal modifiers of the infant gut microbiota: metabolic consequences

Mulligan

Friedman

2017

Journal of Endocrinology

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Transmission of metabolic diseases from mother to child is multifactorial and includes genetic, epigenetic, and environmental influences. Evidence in rodents, humans and non-human primates support the scientific premise that exposure to maternal obesity or high-fat diet during pregnancy creates a long-lasting metabolic signature on the infant innate immune system and the juvenile microbiota which predisposes the offspring to obesity and metabolic diseases. In neonates, gastrointestinal microbes introduced through the mother are noted for their ability to serve as direct inducers/regulators of the infant immune system. Neonates have a limited capacity to initiate an immune response. Thus, disruption of microbial colonization during the early neonatal period results in disrupted postnatal immune responses that highlight the neonatal period as a critical developmental window. Although the mechanisms are poorly understood, increasing evidence suggests that maternal obesity or poor diet influences the development and modulation of the infant liver and other end-organs through direct communication via the portal system, metabolite production, alterations in gut barrier integrity, and the hematopoietic immune cell axis. This review will focus on how maternal obesity and dietary intake influence the composition of the infant gut microbiota and how an imbalance or maladaptation in the microbiota, including changes in early pioneering microbes, might contribute to the programming of offspring metabolism with special emphasis on mechanisms that promote chronic inflammation in the liver. Comprehension of these pathways and mechanisms will elucidate our understanding of developmental programming, and may expand the avenue of opportunities for novel therapeutics.

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“…We consider values of the mutant's growth rate larger or larger or smaller than r = 2 (that of the wild type) motivated by the attention that the fitness effect of resistance has received over the past decade (Andersson and Hughes 2010;Melnyk et al 2015). While resistance mutations typically impair growth to a certain extent (Schrag et al 1997;Reynolds 2000), some can be advantageous even in the absence of the drug (Luo et al 2005;Marcusson et al 2009;Vickers et al 2009;Baker et al 2013;Miskinyte and Gordo 2013;Rodríguez-Verdugo et al 2013). In addition, there is a growing concern regarding the selection for resistance under the nonlethal antibiotic concentrations commonly found in many clinical and natural environments (Gullberg et al 2011;Andersson and Hughes 2014;Larsson 2014;Johnning et al 2015).…”

Section: Resultsmentioning

confidence: 99%

“…Such conditions are not rare in clinical and agricultural settings, where antibiotic gradients occur naturally in wastewater or inside human and animal body compartments (Baquero and Negri 1997;Kümmerer 2004). In addition, recent reports showed that some resistance mutations can be advantageous in the absence of antibiotics (Luo et al 2005;Marcusson et al 2009;Vickers et al 2009;Baker et al 2013;Miskinyte and Gordo 2013;Rodríguez-Verdugo et al 2013). Interestingly, some of these benefits were described to arise as a by-product of adaptation to common circumstances, such as thermal stress (Rodríguez-Verdugo et al 2013), macrophage phagocytosis (Miskinyte and Gordo 2013), or growth impairment caused by previously acquired resistance mutations (Marcusson et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Determinants of Genetic Diversity of Spontaneous Drug Resistance in Bacteria

2016

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Any pathogen population sufficiently large is expected to harbor spontaneous drug-resistant mutants, often responsible for disease relapse after antibiotic therapy. It is seldom appreciated, however, that while larger populations harbor more mutants, the abundance distribution of these mutants is expected to be markedly uneven. This is because a larger population size allows early mutants to expand for longer, exacerbating their predominance in the final mutant subpopulation. Here, we investigate the extent to which this reduction in evenness can constrain the genetic diversity of spontaneous drug resistance in bacteria. Combining theory and experiments, we show that even small variations in growth rate between resistant mutants and the wild type result in orders-ofmagnitude differences in genetic diversity. Indeed, only a slight fitness advantage for the mutant is enough to keep diversity low and independent of population size. These results have important clinical implications. Genetic diversity at antibiotic resistance loci can determine a population's capacity to cope with future challenges (i.e., second-line therapy). We thus revealed an unanticipated way in which the fitness effects of antibiotic resistance can affect the evolvability of pathogens surviving a drug-induced bottleneck. This insight will assist in the fight against multidrug-resistant microbes, as well as contribute to theories aimed at predicting cancer evolution.

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Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages

Cited by 45 publications

References 53 publications

Microscopic and Spectroscopic Analyses of Chlorhexidine Tolerance in Delftia acidovorans Biofilms

Microscopic and Spectroscopic Analyses of Chlorhexidine Tolerance in Delftia acidovorans Biofilms

Maternal modifiers of the infant gut microbiota: metabolic consequences

Determinants of Genetic Diversity of Spontaneous Drug Resistance in Bacteria

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