Heterogeneity of Salmonella-host interactions in infected host tissues

Abstract

Infected host tissues have complex anatomy, diverse cell types, and dynamic inflammation. Traditional infection biology approaches largely ignore this complex host environment and its impact on pathogens, but recent single-cell technologies unravel extensively heterogeneous host-pathogen interactions in vivo. Salmonella are major model pathogens in this field due to the availability of excellent mouse disease models and facile molecular biology. The results show how Salmonella stochastically vary their virulence, exploit differential nutrient availability, experience and respond to widely varying stresses, and have disparate fates ranging from vigorous proliferation to eradication within the same host tissue. Specific Salmonella subsets drive disease progression, while others persist during antimicrobial chemotherapy. Further elucidation of the underlying mechanisms could provide a basis for improved infection control.

Bacterial Heterogeneity and Antibiotic Survival: Understanding and Combatting Persistence and Heteroresistance

“…Both fundamental and clinical studies will need to go hand-inhand with the development of new techniques to study in vivo infection dynamics and to evaluate the direct effect of antibiotic treatment on bacteria at the site of infection. Indeed, while most studies have been conducted on in vitro models, the host environment is far more complex, adding to the pathogens' phenotypic heterogeneity (Bumann and Cunrath, 2017;Meylan et al, 2018). Single-cell approaches are widely used to study population heterogeneity in vitro but are more challenging for in situ (i.e., within the host) analyses (Kreibich and Hardt, 2015).…”

Bacteria under antibiotic attack: Different strategies for evolutionary adaptation

“…The above-mentioned concepts might provide a basis to predict bacterial adaptation to antibiotic stress within a patient, as a function of the local concentrations of nutrients and antibiotics. Problematically however, in vivo environments are extremely complex, heterogeneous, and not well characterized, which considerably complicates the extrapolation of in vitro observations to within-host conditions [45,46]. Indeed, local concentrations of nutrients and antibiotics vary strongly among and even within tissues.…”

A data-based mathematical modelling study to quantify the effects of ciprofloxacin and ampicillin on the within-host dynamics of Salmonella enterica during treatment and relapse

“…Overall, this simulation study shows that phenotypic heterogeneity at the level of two subpopulations is detectable from ITS-based data collected at the level of the entire bacterial population. Each of the horizontal panels (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) represents the fit between one synthetic dataset and the SP-and DP-models in blue and red respectively. The blue and red dots represent the number of standard deviations between the moments of the virtual dataset and the mean value of 500 bootstrapped datasets generated from the best parameter set in the SP and DP model respectively.…”

“…The effect of different antibiotics on bacterial dynamics has been studied extensively in vitro, in optimally and homogeneously growing bacterial populations harvested from exponentially growing cultures [5]. Conclusions drawn from these studies provide insights into the mode of action of different antibiotic agents on their bacterial targets; however, their clinical relevance remains unknown, as in vivo bacterial populations are characterised by heterogeneity in their growth and dissemination dynamics [6][7][8][9]. Upon successful colonisation, in vivo bacterial behaviour is multifactorially shaped by nutrient availability [6,10], host immunity [11][12][13], spatial arrangement of the infectious foci [14], and host cell composition in the immediate bacterial vicinity [15][16].…”