Profiling Mycobacterium Ulcerans: Sporulation, Survival Strategy and Response to Environmental Factors

Figures & data

Figure 1. Proposed transmission patterns of Mycobacterium ulcerans showing the role of the aquatic ecosystems and animals in the transmission of M. ulcerans from the environment to humans.

(Figure designed by authors: ¹[5], ²[7], ³[13], ⁴[38], ⁵[72], ⁶[11] and ⁷[15]).

Figure 2. M. ulcerans response mechanisms to external stress factors.

(A) Environmental stress factors that affect the survival of M. ulcerans and their sources. (B) Possible stress response mechanisms that are mounted by mycobacterium in response to environmental stress. (C) Stress response mechanisms or an alteration of cellular processes under stress conditions that may result in dormancy or the formation of distinct cell types such as endospores or cellular aggregates such as biofilms.

Figure 3. A schematic-proposed overview of the sporulation process in M. ulcerans.

The diagram illustrates only key morphological stages of the cycle; The cell differentiates into a smaller prespore, which goes through several stages, accompanied by differential gene regulation to form a mature spore that is highly resistant to stress.

Table 1. Sporulation associated markers.

Strain	Sporulation markers	Detection method	Ref.
Mycobacterium marinum	spoVK, cotSA, yrbC, spoVE, Soj, spoIIIE, spo0A, spoIIAB, sigA, sigF	Dot-blot hybridization	[68]
M. avium Subsp. Paratuberculosis	MAP 122 (kinB^+), MAP 0260 (kinA^+), phoR (kinC^+), MAP 1002c (spo0A), MAP 3780 (spo0B)	PCR	[30]
M. tuberculosis	sigF	PCR	[79]
Other spore forming environmental pathogens
Bacillus spp.	cotA, crbB, cotS, sspA, sspE, sspA, sotF, coxA, cspD, Hbs, phoA, sleB, spsK, spoVK, sigF, sigA, spoIIIE, sotsA, spsK, spo0A, Soj, sotD	Proteomics analysis (SDS-PAGE, Mass Spectrometry), Transcriptional Profiling	[71,73]
Clostridium spp.	spoVS, spoIIE, sigF, spo0A, ftsAZ, aad, ctfa, ctfb, spoIIR, spoIIQ, spoIIIG, spoIIAA, spoIIAB, spoIIGA, spoIIIJ	DNA microarray	[74,75]
Streptomyces coelicolor	whiG, whiL, whiA, whiB, parAB, ftsZ, hupS	Transcriptional analysis	[76,77,78]

PhanzuDM , MahemaRL , SuykerbuykPet al.Mycobacterium ulcerans infection (Buruli ulcer) on the face: a comparative analysis of 13 clinically suspected cases from the Democratic Republic of Congo. Am. J. Trop. Med. Hyg.85(6), 1100–1105 (2011).

 PubMed Web of Science ®Google Scholar

BoccarossaA , DegnonviH , BrouTYet al.A combined field study of Buruli ulcer disease in southeast Benin proposing preventive strategies based on epidemiological, geographic, behavioural and environmental analyses. PLOS Glob. Public Heal.2(1), e0000095 (2022).

 PubMedGoogle Scholar

WuJ , TschakertP , KlutseE , FerringDet al.Buruli ulcer disease and its association with land cover in Southwestern Ghana. PLOS Negl. Trop. Dis.9(6), e0003840 (2015).

 PubMed Web of Science ®Google Scholar

MerrittRW , BenbowME , SmallPLC. Unraveling an emerging disease associated with disturbed aquatic environments: the case of Buruli ulcer. Front. Ecol. Environ.8(1), e2660 (2005).

 Google Scholar

Ramos-SilvaP , SerranoM , HenriquesAO. From root to tips: sporulation evolution and specialization in Bacillus subtilis and the intestinal Pathogen Clostridioides difficile. Mol. Biol. Evol.36(12), 2714–2736 (2019).

 PubMed Web of Science ®Google Scholar

MarsollierL , RobertR , AubryJet al.Aquatic insects as a vector for Mycobacterium ulcerans. Appl. Environ. Microbiol.68(9), 4623–4628 (2002).

 PubMed Web of Science ®Google Scholar

BolzM , RuggliN , RufMT , RicklinME , ZimmerG , PluschkeG. Experimental infection of the pig with Mycobacterium ulcerans: a novel model for studying the pathogenesis of Buruli ulcer disease. PLOS Negl. Trop. Dis.8(7), e2968 (2014).

 PubMed Web of Science ®Google Scholar

TanIS , RamamurthiKS. Spore formation in Bacillus subtilis. Environ. Microbiol. Rep.6(3), 212–225 (2014).

 PubMed Web of Science ®Google Scholar

StinearTP , SeemannT , PidotSet al.Reductive evolution and niche adaptation inferred from the genome of Mycobacterium ulcerans, the causative agent of Buruli ulcer. Genome Res.17(2), 192–200 (2007).

 PubMed Web of Science ®Google Scholar

DeMaioJ , ZhangY , KoCet al.Mycobacterium tuberculosis sigF is part of a gene cluster with similarities to the Bacillus subtilis sigF and sigB operons.. Tuber. Lung Dis.78(1), 3–12 (1997).

 PubMedGoogle Scholar

MartínezA , TorelloS , KolterR. Sliding motility in mycobacteria. J. Bacteriol.181(23), 7331–7338 (1999).

 PubMed Web of Science ®Google Scholar

HilbertDW , PiggotPJ. Compartmentalization of gene expression during Bacillus subtilis spore formation. Microbiol. Mol. Biol. Rev.68(2), 234–262 (2004).

 PubMed Web of Science ®Google Scholar

EichenbergerP , JensenST , ConlonEMet al.The σE regulon and the identification of additional sporulation genes in Bacillus subtilis. J. Mol. Biol.327(5), 945–972 (2003).

 PubMed Web of Science ®Google Scholar

EdwardsAN , McbrideSM. Initiation of sporulation in Clostridium difficile: a twist on the classic model. FEMS Microbiol. Lett.358(2), 110–118 (2014).

 PubMed Web of Science ®Google Scholar

GalperinMY , MekhedovSL , PuigboP , SmirnovS , WolfYI , RigdenDJ. Genomic determinants of sporulation in Bacilli and Clostridia: towards the minimal set of sporulation-specific genes. Environ. Microbiol.14(11), 2870–2890 (2012).

 PubMed Web of Science ®Google Scholar

SprusanskyO , ZhouL , JordanSet al.Identification of three new genes involved in morphogenesis and antibiotic production in Streptomyces coelicolor.. J. Bacteriol.185(20), 6147–6157 (2003).

 PubMed Web of Science ®Google Scholar

SalernoP , PerssonJ , BuccaGet al.Identification of new developmentally regulated genes involved in Streptomyces coelicolor sporulation.BMC Microbiol.13(281), (2013).

 PubMedGoogle Scholar