Mycolicibacterium fortuitum genomic epidemiology, resistome and virulome

Abstract

BACKGROUND Mycolicibacterium fortuitum is an opportunistic pathogen associated with human and animal infection worldwide. Studies concerning this species are mainly represented by case reports, some of them addressing drug susceptibility with a focus on a specific geographic region, so there is a gap in relation to the global epidemiological scenario.OBJECTIVES We aimed determine the global epidemiological scenario of M. fortuitum and analyse its traits associated with pathogenicity.METHODS Based on publicly available genomes of M. fortuitum and a genome from Brazil (this study), we performed a genomic epidemiology analysis and in silico and in vitro characterisation of the resistome and virulome of this species.FINDINGS Three main clusters were defined, one including isolates from the environment, human and animal infections recovered over nearly a century. An apparent intrinsic resistome comprises mechanisms associated with macrolides, betalactams, aminoglycosides and antitubercular drugs such as rifampin. Besides, the virulome presented Type VII secretion systems (T7SS), including ESX-1, ESX-3, ESX-4 and ESX-4-bis, some of which play a role on the virulence of Mycobacteriaceae species.MAIN CONCLUSIONS Here, M. fortuitum was revealed as a reservoir of an expressive intrinsic resistome, as well as a virulome that may contribute to its success as a global opportunist pathogen.

Comparative genome analysis reveals high-level drug resistance markers in a clinical isolate of Mycobacterium fortuitum subsp. fortuitum MF GZ001

“…These genes may only be found in the MF GZ001 strain and M. tuberculosis H37Rv. Recently, Luo et al, reported that the secretion proteins locus ESX-1, ESX-3, and ESX-5 are crucial for virulence in M. tuberculosis (Luo et al, 2022) and were found in the MF GZ001 strain which is consistent with the previous report (Gharbi et al, 2021;Morgado et al, 2022b). Therefore, the MF GZ001 genome sequence will provide insights into M. fortuitum complex potential pathogenesis.…”

“…We have reported a mutation in a distinctive gene aph (3")-Ic that is related to streptomycin resistance which is consistent with other studies (Morgado et al, 2022a). The aph (3")-Ic distinctive gene was first reported in environmental M. fortuitum and later in clinical isolates as well (Ramon-Garcia et al, 2006;Morgado et al, 2022b). We anticipate that further investigation of the novel SNPs in iniA, iniC, ribD, pncA, and aph (3")-Ic detected in this study are necessary to explore their role in the development of resistance.…”

Multidrug-resistant Mycolicibacterium fortuitum infection in a companion cat (Felis silvestris catus) in Brazil

“…In addition, infections caused by M. fortuitum are characterized by high resistance to antibiotics, such as aminoglycosides, beta-lactams, macrolides, rifamycins, and tetracyclines [ 13–15 ]. Recently, a genomic study revealed that a set of genes associated with resistance to these antibiotics (a ph(3’’)-Ic , aac(2’)-Ib , arr -1, bla F, erm 39, rbp A, rox , and tap ) appears to be ubiquitous in M. fortuitum species [ 16 ]. Since treatment of mycobacteriosis is long-term, isolation and antibiotic susceptibility assays are recommended to avoid delays in treatment [ 9–11 ].…”

Evolution shapes metabolic function and niche-specific antimicrobial targets in pathobionts

“…It is important to note that in Figure 3 there is one group of pathobiont pairs that are more genetically distant from each other. For every pair in this group, one bacterium in the pair is Mycolicibacterium fortuitum , which is an opportunistic pathogen that is responsible for skin and bone infections belonging to the actinomycetia taxonomic class 34 . In this group, the bacteria paired with Mycolicibacterium fortuitum are: seven different Bacillus species, two Vibrio species, two Acinetobacter species, two Burkholderia species, and one Providencia, Enterobacter , and Stenotrophomonas species.…”