Culturomics Discloses Anti-Tubercular Enterococci Exclusive of Pulmonary Tuberculosis: A Preliminary Report

Abstract

Mycobacterium tuberculosis causes pulmonary tuberculosis, a deadly infection of which the clinical expression and prognosis are not fully understood at the individual level, apart from genetic susceptibility traits. We investigated whether individual gut microbiota may correlate with pulmonary tuberculosis status. Culturomics investigations of gut microbiota in two pulmonary tuberculosis patients and two controls in Burkina Faso found 60 different bacterial species in patients and 97 in controls, including 45 in common. Further analysis of the results at the individual level indicated seven bacteria, including Enterococcus mundtii and Enterococcus casseliflavus, which were exclusively cultured in controls. Blind quantitative PCR-based exploration of faeces samples in two cohorts in Burkina Faso and in France confirmed a nonsignificant association of E. mundtii and E. casseliflavus with controls. Further in vitro explorations found four E. mundtii and E. casseliflavus strains inhibiting the growth of M. tuberculosis strains representative of four different lineages as well as Mycobacterium africanum, Mycobacterium canettii, and Mycobacterium bovis, in an inoculum-dependent manner. Heat-killed E. mundtii or E. casseliflavus were ineffective. These unprecedented observations of direct interactions between gut E. mundtii and E. casseliflavus with M. tuberculosis complex mycobacteria suggest that gut microbiota may modulate the expression of pulmonary tuberculosis.

The Enterococcus secretome inhibits the growth of Mycobacterium tuberculosis complex mycobacteria

“…The fact that E. mundtii inhibited the growth of some MTC species had been previously described in our laboratory [23], and the data reported here broadened such previous observations by cross-incorporating a set of E. mundtii strains and MTC species using a standardized agar well diffusion assay to compare cross-inhibition values. Accordingly, we observed that both E. mundtii suspensions and derived lyophilized culture supernatants inhibited the growth of M. tuberculosis, M. africanum, M. bovis and M. canettii.…”

“…The fact that E. mundtii inhibited the growth of some MTC species had been previously described in our laboratory [23], and the data reported here broadened such previous observations by cross-incorporating a set of E. mundtii strains and MTC species using a standardized agar well diffusion assay to compare cross-inhibition values.…”

“…Recently, we reported the in vitro inhibitory effect of Enterococcus mundtii against MTC species [ 23 ]. Here, we further investigated the experimental anti-tuberculosis activity of different Enterococcus species to characterize and explore the inhibition spectrum of the Enterococcus secretome against some MTC representative species.…”

Wildlife Symbiotic Bacteria Are Indicators of the Health Status of the Host and Its Ecosystem

“…As reported in our previous work ( 23 ), lactobacilli from the TB-free estates (group 1) significantly inhibited M. bovis BCG, probably through the combination of multiple synergistic metabolites such as organic acids, hydrogen peroxide, ethanol, and unmodified two-peptide bacteriocins. Enterococci from the TB estates (group 2) showed a much lower reduction of BCG survival, which contradicts some authors who demonstrated the antimycobacterial effect of enterococci ( 57 ). Strikingly, the P. acidilactici strain (C5) from the TB-free group showed a much higher antimycobacterial activity than that of the P. acidilactici strain (R91) isolated from the estate with a high TB prevalence.…”

Causal associations of gut microbiota and pulmonary tuberculosis: a two-sample Mendelian randomization study

“…Significant alterations have been observed in the gut microbiota composition of PTB patients compared to healthy individuals ( Hu et al, 2019 ). In Burkina Faso, the growth of M. tuberculosis strains in vitro was found to be inhibited by two Firmicutes species, namely E. casseliflavus and E. mundtii , which were isolated from patients who tested negative for TB ( Fellag et al, 2020 ). A study conducted in western China revealed a direct relationship between the gut microbiota and the number of peripheral CD4 + T cells in individuals with tuberculosis ( Luo et al, 2017 ).…”