High-Throughput Carbon Substrate Profiling of Mycobacterium ulcerans Suggests Potential Environmental Reservoirs

Abstract

BackgroundMycobacterium ulcerans is a close derivative of Mycobacterium marinum and the agent of Buruli ulcer in some tropical countries. Epidemiological and environmental studies pointed towards stagnant water ecosystems as potential sources of M. ulcerans, yet the ultimate reservoirs remain elusive. We hypothesized that carbon substrate determination may help elucidating the spectrum of potential reservoirs.Methodology/Principal findingsIn a first step, high-throughput phenotype microarray Biolog was used to profile carbon substrates in one M. marinum and five M. ulcerans strains. A total of 131/190 (69%) carbon substrates were metabolized by at least one M. ulcerans strain, including 28/190 (15%) carbon substrates metabolized by all five M. ulcerans strains of which 21 substrates were also metabolized by M. marinum. In a second step, 131 carbon substrates were investigated, through a bibliographical search, for their known environmental sources including plants, fruits and vegetables, bacteria, algae, fungi, nematodes, mollusks, mammals, insects and the inanimate environment. This analysis yielded significant association of M. ulcerans with bacteria (p = 0.000), fungi (p = 0.001), algae (p = 0.003) and mollusks (p = 0.007). In a third step, the Medline database was cross-searched for bacteria, fungi, mollusks and algae as potential sources of carbon substrates metabolized by all tested M. ulcerans; it indicated that 57% of M. ulcerans substrates were associated with bacteria, 18% with alga, 11% with mollusks and 7% with fungi.ConclusionsThis first report of high-throughput carbon substrate utilization by M. ulcerans would help designing media to isolate and grow this pathogen. Furthermore, the presented data suggest that potential M. ulcerans environmental reservoirs might be related to micro-habitats where bacteria, fungi, algae and mollusks are abundant. This should be followed by targeted investigations in Buruli ulcer endemic regions.

A protocol for culturing environmental strains of the Buruli ulcer agent, Mycobacterium ulcerans

“…The degradation products serve as an important nutrient source for bacteria in the nature 51 . M. ulcerans may obtain energy and carbon from the degradation of plant saccharides which were demonstrated to stimulate M. ulcerans growth in vitro 14 , 53 . It was recently shown that chitin promoted growth of M. ulcerans 43 .…”

Buruli Ulcer, a Prototype for Ecosystem-Related Infection, Caused by Mycobacterium ulcerans

“…In a recent high-throughput carbon substrate profile of M. ulcerans in our laboratory, we found a significant association between the M. ulcerans core biologome and bacteria, fungi, algae, and mollusks. We concluded that environmental M. ulcerans research should increase its focus on fungi, algae, and mollusks, because they contain the nutrients necessary for the survival of M. ulcerans (211).…”

“…Buruli ulcer has also been encountered in aquatic invertebrates, mosquitoes (13, 16, 19, 91, 107, 113, 139, 141, 149, 150, 152-154, 156, 193), crayfish (108), amoeba, mollusks, crustaceans, annelida (29,40,141,153), aerosols, water, biofilm, moss, detritus, feces, plants, and soil (13,29,39,63,93,106,107,112,113,(144)(145)(146)(147)210). The hypothesis most advanced to aggregate data issuing from the investigations on the environment is that M. ulcerans may be part of a food chain (211,212).…”

Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes

“…Differential metabolomics analysis is carried out for detection of eventual interaction of compound 1 with cellular subsystems. By using Phenotype MicroArray-based approach 16 , 17 , the differential analysis of B. cereus ATCC 14579 metabolism shows selective inhibition to several carbon sources. The associated metabolic pathways are identified according to the KEGG (Kyoto Encyclopedia of Genes and Genomes) database and hierarchical mapped (Supplementary Fig 9 ).…”