Dysbiosis-Associated Change in Host Metabolism Generates Lactate to Support Salmonella Growth

Abstract

The authors would like to clarify that several experiments in the paper as detailed here were performed simultaneously. Specifically, the histology slides represented in Figures 1G, 2E, and 3H were analyzed by a blinded reviewer and quantified using the same pathology scale. The experiments yielding data on intestinal permeability (Figures 3D and 5B) and ELISA data (Figures 1E, 1F, 2B, 3G, and 3I) were performed simultaneously to minimize inter-experimental error. The relevant comparisons (e.g., age, genotype, SPF/germ-free) were presented in separate figures/panels to facilitate the narrative of the manuscript, but the statistical analysis was performed and presented based on analysis of the entire dataset. Additionally, the sentence ''Mice were deprived of food 4 hr prior to and both food and water 4 hr following an oral gavage using 200 ml of 0.8 mg/ml FITC-dextran'' should state ''80 mg/ml FITC-dextran.'' The authors apologize for this error, and it has been corrected online.

Oxygen‐dependent regulation of SPI1 type three secretion system by small RNAs in Salmonella enterica serovar Typhimurium

“…These short‐chain fatty acids are at their highest concentration in the distal small intestine (Argenzio et al , ; Cummings et al , ; Macfarlane et al , ). In contrast, butyrate, produced by the strict anaerobes in the colon, negatively regulates SPI1 expression (Gantois et al , ; Bronner et al , ; Gillis et al , ). We believe that these concentration gradients are such that SPI1 is optimally expressed in the distal small intestine.…”

Metabolism at the centre of the host–microbe relationship

“…Antibiotic treatment-induced dysbiosis can have widereaching effects, for example on inflammation, infection and responses to vaccination [70][71][72]. Antibiotics have been shown to affect SCFA-producing bacteria causing a decrease in SCFA abundance [73,74].…”

“…Salmonella spp. Changes in enterocyte metabolism were found to generate lactate which, along with the increase in oxygen, Salmonella could use as an energy source with oxygen as the final electron acceptor [70]. Neutrophils, and the inflammation induced, release a large amount of electron acceptors, such as tetrathionate and nitrate, which fuel Salmonella metabolism, allowing their expansion while altering the gut microbial composition, including the depletion of Clostridia spp.…”

Mycobacterium tuberculosis requires glyoxylate shunt and reverse methylcitrate cycle for lactate and pyruvate metabolism

“…Many pathogens can use lactate as a carbon source in vitro . It is well known that Neisseria meningitidis relies on host‐derived lactate to be virulent (Exley et al , ; ; Sigurlasdottir et al , ) and recently, it has been reported that host‐derived lactate also supports Salmonella enterica (Gillis et al , ) virulence. Mtb can use lactate or pyruvate as sole carbon source in vitro (Youmans and Youmans, ) and Mtb LldD2/Rv1872c lactate dehydrogenase is essential for replication in human‐derived macrophages (Billig et al , ).…”