Mycobacterium colombiense
Classification
Higher order taxa
Bacteria; Actinobacteria; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium [1].
Species
Mycobacterium colombiense
Description and significance
Mycobacterium colombiense is a novel species within the Mycobacterium avium complex (MAC), a group of Gram positive, non-tuberculosis bacteria that have been found in soil and water systems worldwide [2]. Members of the species M.colombiense are opportunistic pathogens that have been found in immunocompromised individuals, specifically patients who suffer from the HIV/AIDS, lymphadenopathy, and pulmonary infections [2]. M. colombiense exhibits unique metabolic characteristics due to its production of urease and consistent mycolic acid patterns [3] and has been distinguished by its ability to form biofilms on non-biological surfaces [2]. The presence of M. colombiense in water systems throughout hospitals in urban areas poses a greater risk for those being treated in clinical environments [4]. M. colombiense exhibits distinguished genotypic characteristics, including a unique 16s rDNA sequence and lack of genes coding for heat shock proteins. Additionally, the bacterium has cell wall lipids that prevent human immune cell function [5]. Such findings could potentially be a step towards species-specific diagnostic tools, making treatment of infected individuals more accessible [5]].
Genome structure
The genome of the CECT 3035 strain of M. colombiense isolated from Colombian HIV patients was sequenced in 2011. The genome of this strain is one DNA molecule consisting of 5.6 Mb and encoding for 5,230 genes [6]. Since the initial sequencing of CECT 3035 was completed, subsequent strains of M. colombiense have been sequenced revealing an average GC (guanine cytosine) and AT (adenine thymine) content of 68% and 32%, respectively. The average number of genes is 5,206, of which 5,105 encode for proteins [7]. Further genomic analysis indicates the presence of 45 genomic islands (group of genes acquired from other cells) containing 320 genes. Of these 45 islands, 9 are classified as pathogenic islands [5]. Genes encoding for proteins that are induced to protect against oxidative stress, and a gene encoding for a urease accessory protein are part of the genome.
A recent study seeking to identify the genes involved in pathogenesis of M. colombiense compared its genome to the genome of the well-studied Mycobacterium tuberculosis. In both of these bacteria, genes coding for the same cell wall glycolipids, genes coding for proteins involved in protection against reactive oxygen species, and genes coding for proteins involved in exporting lipoproteins that manipulate human immune cell response were discovered [5]. Both species have the same two-component adaptation systems that are involved in essential virulence mechanisms. There are a few potentially important genomic differences that could help explain the opportunistic nature of infections caused by M. colombiense, in comparison to the more pathogenic nature of M. tuberculosis [5]. One difference is M. colombiense lacks a gene coding for a heat shock protein induced in M. tuberculosis when the concentration of oxygen is low. M. colombiense also lacks genes coding for cell wall lipids that prevent human immune cells from fusing and killing the bacterial cells [5].
M. colombiense has a unique 16S sequence that differentiates it from other species of the MAC. Isolates of M. colombiense from Colombian HIV positive patients were found to have a 16S-23S internal transcribed spacer sequence (ITS 1) called MAC-X, specifically unique to this strain [3]. The isolates were confirmed as part of the MAC complex but tested negative with the species-specific probes. DNA-DNA hybridization results comparing M. colombiense and the other MAC species varied from 12%- 40%, indicating results that are consistent with M. colombiense being a separate species [3].
Cell structure and metabolism
The metabolism of M. colombiense allows it to live and multiply in oligotrophic environments [4]. The cell structure and metabolism of M. colombiense that distinguishes it from others in the MAC complex centers around its biofilm formation and urease activity. Colony morphology varies depending on biofilm formation. Both smooth and rough appearances of M. colombiense have been documented. Furthermore, the smooth colony morphology of M. colombiense correlates to a higher motility on hydrophilic media while rough variants reduce motility on hydrophilic surfaces [2]. The bacteria’s colony appearance and motility also is inconsistent; cases of pigmented and nonpigmented M. colombiense have been recorded, as well as cases where the bacteria is motile and nonmotile, with the latter being acid fast [3]. M. colombiense has a mycolic acid pattern unique from other mycobacteria as its peaks do not resemble a bell-shape [3].
Ecology
With the ability to form biofilms, M. colombiense has a slight affinity to moist environments and has the ability to reproduce in low nutrient, chlorinated environments like water pipes and hospital hot water systems [4]. While M. colombiense is often described to be a slow grower, visible growth of its rough colonies begins to appear at 3 weeks at 20 to 37 degrees Celsius. At room temperature, M. colombiense will show catalase activity, yet it does not produce niacin, hydrolyze Tween, or have acid phosphatase activity [3].
Pathology and clinical significance
M. colombiense has been implicated as a pathogen responsible for various diseases that affect both immunocompetent and immunocompromised individuals [8,9]. Lymphadenitis, particularly in the pediatric population, has commonly been attributed to M. colombiense [8]. M. colombiense has also been named as the cause of lymphadenopathy in a three-year old girl, marking the first case of this disease in a pediatric immunocompetent patient [9]. Furthermore, one particular case implicates M. colombiense as the cause of a rare cutaneous infection in a seventeen year old patient, the infection characterized by deep erythemas, some with a scale texture, and red nodules, some oozing discharge [10].
Multiple studies have also correlated M. colombiense with HIV and AIDS. Much of the genetic information known about M. colombiense came from studies of Colombian HIV/AIDS patients [8]. One study of pediatric patients who contracted lymphadenitis due to non-tuberculous mycobacterium revealed that antibiotic susceptibility isolates of M. colombiense are closely related to isolates found in AIDS patients infected by the MAC bacteria [8].
The presence of urease has been identified as a key virulence factor in assisting bacteria in causing diseases in humans [5]. In mutant strains of M. colombiense lacking the genes for urease accessory proteins, the bacterium showed reduced multiplication within macrophages. This finding suggests that the urease proteins are important for the bacterium to survive and replicate within the immune system [5].
Current and Future Research
The correlation between HIV/AIDS and M. colombiense is ambiguous and therefore a key topic of current research into this strain of bacterium. Urease production is an important virulence factor that contributes to pathogenicity and a unique characteristic of M. colombiense that may shed light on its relationship with immunocompromised individuals [5]. In addition, because of the similarities between M. colombiense and other members of the MAC such as M. tuberculosis, improved species-specific diagnostic tools are necessary to construct differential diagnoses for identification of rarer species that may cause disease and initiation of proper treatment [9, 10].
Reports of M. colombiense motility are inconsistent, prompting more research into this area of study. Description of M. colombiense motility ranges from non-motile to variable motility depending on culture conditions and morphology [2, 3]. Case studies on clinical implications of M. colombiense infection describe the presence of non-pigmented colonies with a rough morphology, but make no mention of a smooth, pigmented appearance [3, 10]. However, smooth colony morphology has been associated with higher virulence of MAC bacteria [2].
References
1. “Mycobacterium avium complex”- MicrobeWiki. Retrieved Sepember 21, 2016, from https://microbewiki.kenyon.edu/index.php/Mycobacterium_avium_complex
2. Maya-Hoyos, M., Leguizamon, J., Marino-Ramirez, L., & Soto, C.Y. 2015. Sliding Motility, Biofilm Formation, and Glycopeptidolipid Production in Mycobacterium Colombiense Strains. BioMed Research International 2015: 1-11.
3. Murcia, M. I., Tortoli, E., Menendez, M.C., Palenque, E., and Garcia, M.J. 2006. Mycobacterium Colombiense Sp. Nov., a Novel Member of the Mycobacterium Avium Complex and Description of MAC-X as a New ITS Genetic Variant. International Journal of Systematic and Evolutionary Microbiology 56: 2049–54.
4. Khosravi, A. D., Hashemi Shahraki, A., Hashemzadeh, M., Sheini Mehrabzadeh, R., & Teimoori, A. 2016. Prevalence of Non-Tuberculous Mycobacteria in Hospital Waters of Major Cities of Khuzestan Province, Iran. Frontiers in Cellular and Infection Microbiology 6(42): 1-8.
5. Gonzalez-Perez, MN., Murcia, M.I., Parra-Lopez, C., Blom, J., & Tauch, A. 2016. Deciphering the Virulence Factors of the Opportunistic Pathogen Mycobacterium colombiense. New Microbes and New Infections 14: 98-105.
6. Gonzalez-Perez, M., Murcia, M.I., Landsman, D., Jordan, IK., Marino-Ramirez, L. 2011. Genome Sequence of the Mycobacterium colombiense Type Strain, CECT 3035. Journal of Bacteriology 193: 5866-5867.
7. National Center for Biotechnology Information. N.d. Organism Overview; TXID=1041522, https://www.ncbi.nlm.nih.gov/genome/?term=txid1041522[Organism:noexp]
8. Hazra, R., C.D. Robson, A.R. Perez-Atayde, & R.N. Husson, 1999. Lymphadenitis due to nontuberculous mycobacteria in children: presentation and response to therapy. Clin. Infect. Dis. 28:123-129.
9. Esparcia, O., Navarro, F., Quer, M., & Coll, P. 2008. Lymphadenopathy Caused by Mycobacterium Colombiense. Journal of Clinical Microbiology, 46(5):1885–87. doi:10.1128/JCM.01441-07.
10. Gao, W., Chen, H., Jiang, H., Wang, Q., Tang, M., & Wang, H. 2014. Disseminated Cutaneous Infection Caused by Mycobacterium colombiense. Acta Dermato Venereologica, 94(6): 727–728.
Edited by [Micayla Freehan, Ashley Stern, Emily Thoi, and Bruce Wayne], students of Jennifer Talbot for [1], 2016, [2]
