Mycobacterium kansasii

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Classification

Domain: Bacteria; Phylum: Actinomycete; Class: Actinomycetia; Order: Mycobacteriales; Family: Mycobacteriaceae; Genus: Mycobacterium; Species: kansasii

Species

NCBI: Taxonomy

Mycobacterium kansasii

Description and Significance

Mycobacterium kansasii account for most non-tuberculous mycobacterium diseases (NTM). Due to its close relation to M. tuberculosis, M. kansasii is often under-represented and misdiagnosed. Fortunately, the treatment of pulmonary tuberculosis is effective against M. kansasii disease. First isolated in 1953, scientists found the bacterium to be a gram positive, non-motile, acid fast rod that is slightly longer than that of M. tuberculosis. Because of the growing number of immune deficient people and presence in health care centers, M. kansasii is a growing health concern. Diagnosis is often difficult and treatment can become time consuming and expensive.

Initially, this bacterium was named yellow bacillus due to its unique color. When M. kansasii is grown in light conditions it produces a bright yellow color that is not present in colonies formed under dark low oxygen conditions. This color change, also called photochromogenicity, develops due to the production and break down of beta-carotene crystals within the bacterium. Caratenoids are one of the most abundant types of pigments formed in nature.

Genome Structure

The genome of M. kansasii is organized into a single circular chromosome. This chromosome contains the bacterium's entire genetic material, including both essential genes for survival and virulence determinants. Analysis of the M. kansasii genome has identified several virulence factors that contribute to its pathogenicity. These include genes encoding cell wall-associated proteins, secretion systems, and factors involved in host immune evasion. Understanding the genetic basis of virulence can inform the development of targeted therapies and vaccines. Studies of its genome often employ a three-pronged computational strategy. This uses alignment fraction-average nucleotide identity, genome-to-genome distance, and core-genome phylogeny, has been used to refine the taxonomic structure of the M. kansasii complex. This approach, complemented by the analysis of five canonical taxonomic markers (16S rRNA, hsp65, rpoB, tuf genes, and the 16S-23S rRNA intergenic spacer region), has provided a more complete understanding of the genetic diversity within the complex.


Like other bacterial species, M. kansasii exhibits genomic variation both within and between strains. This variation can arise through mechanisms such as point mutations, insertions, deletions, and horizontal gene transfer. Studying genomic variation can provide insights into the evolution and adaptation of M. kansasii to different host environments and clinical settings.

Comparative genomics studies show the genetic relationships between M. kansasii and other mycobacterial species particularly its relationship to Mycobacterium Kansasii. By comparing the genomes of different strains, researchers can identify conserved genes, lineage-specific genes, and genomic regions associated with particular phenotypes or clinical outcomes. These comparative analyses contribute to our understanding of the evolutionary history and pathogenic potential of M. kansasii. Advances in genomic sequencing technologies have facilitated the study of M. kansasii's genome structure and function. High-throughput sequencing techniques, such as whole-genome sequencing and comparative genomics, enable comprehensive analyses of genetic variation and gene expression patterns. These genomic tools have broadened our understanding of Mycobacterium kansasii's biology and pathogenesis, with implications for diagnosis, treatment, and control strategies.

Cell Structure, Metabolism and Life Cycle

Metabolism

M. kansasii is an aerobic organism, meaning it requires oxygen for its metabolic processes. It is capable of metabolizing a variety of organic compounds, including lipids, sugars, and alcohols. This versatility in metabolism allows it to survive and thrive in diverse environments, including soil and water sources. It is capable of utilizing a variety of carbon sources for growth and energy production. These include carbohydrates such as glucose, fructose, and glycerol, as well as fatty acids, amino acids, and organic acids. The ability to metabolize a diverse array of carbon sources is essential for its survival in different environmental niches and during infection within host tissues. M. kansasii is an aerobic organism, meaning it requires oxygen for its respiratory metabolism. It utilizes oxidative phosphorylation to generate ATP, the primary energy currency of the cell. During this process, electrons derived from the oxidation of carbon sources are transferred through a series of electron carriers embedded in the plasma membrane, ultimately driving the synthesis of ATP by ATP synthase. M. kansasii possesses a robust lipid metabolism, allowing it to utilize lipids as carbon and energy sources. Lipids serve as important reservoirs of energy and carbon for the bacteria, particularly during conditions of nutrient limitation or stress. Mycobacteria are known for their ability to degrade complex lipids, such as triglycerides and cholesterol, through the action of specialized enzymes and lipid transport systems. Like other bacteria, M. kansasii requires nitrogen for the synthesis of proteins, nucleic acids, and other essential biomolecules. It can assimilate nitrogen from various sources, including ammonium ions, amino acids, and nitrogenous compounds present in the environment. Nitrogen metabolism is tightly regulated to ensure optimal growth and adaptation to changing nutrient conditions.


Life Cycle

The life cycle of M.kansasii involves several stages, including transmission, colonization, and disease progression. The life cycle of M. kansasii begins with transmission from an infected source to a susceptible host. Transmission primarily occurs through the inhalation of aerosolized droplets containing the bacteria, which can originate from environmental reservoirs or individuals with active or latent infections. Sources of contamination may include soil, water, and fomites contaminated with M. kansasii. Upon inhalation, M. kansasii colonizes the respiratory tract, particularly the lungs, where it establishes infection. The bacteria adhere to and invade the epithelial cells lining the airways, allowing them to evade host immune defenses and establish a niche for replication. Colonization may result in asymptomatic carriage or lead to the development of active disease, depending on the host's immune status and other factors. In some cases, M. kansasii may remain dormant within the host for extended periods, a state known as latency. During latency, the bacteria persist in a non-replicating state, evading immune surveillance and antibiotic therapy. Latent infections may remain asymptomatic or progress to active disease upon reactivation, triggered by factors such as immunosuppression, aging, or comorbidities that compromise host immunity. M. kansasii infections pose public health challenges due to their potential for person-to-person transmission, environmental persistence, and variable clinical outcomes. More research needs to be done on the life cycle of it’s life cycle while in municipal water.

Ecology and Pathogenesis

M. kansasii has been cultured in many countries including Australia, Brazil, United States, Canada, and in parts of Europe. In the United States, M. kansasii is often found in midwestern and southwestern states including Texas. Like most other Non-Tuberculosis Mycobacterium (NTM) infections, infection occurs in humans through inhalation of the bacterium in aerosols. However, this bacterium can be found in drinking water, natural waters, pipes/plumbing, and in soils. Though most studies present human infection case studies, M. kansasii is an opportunistic pathogen and has the ability to infect other organisms. Statistically, infection is more likely to occur in urban areas rather than rural areas; possibly due to an abundance of dirt in the air from mining or farming practices.

Because of the similarities to Tuberculosis, the symptoms are often very similar. Patients often present with a cough and sputum production, fever, chills, night sweats, and weight loss. Mycobacterium kansasii causes most episodes of non-tuberculous systemic disease and can often present in patients with an underlying pulmonary disease or immune deficiency. Because of the presence of similar symptoms, it is likely that many cases of M. kansasii are misdiagnosed as Tuberculosis. Furthermore, M. kansasii can cause a false positive on a tuberculosis skin test. Diagnosis by culture and virulence factors are also inadequate due to the bacterium's slow growth, often taking greater than 7 days to culture, and due to the absence of virulence factors. Therefore, a diagnosis is often made through specific PCR tests and radiology. M. kansasii microbial clusters are often visible in infected patient scans of the lungs.

The standard initial treatment regimen for M. kansasii infections include a combination of three antibiotics: rifampicin, isoniazid, and ethambutol. These drugs are initially administered daily for 18 to 24 months. After completing the initial phase of treatment, patients may transition to a continuation phase, which typically involves the same combination of antibiotics but at reduced dosages. The continuation phase may last an additional 9 to 15 months, for a total treatment duration of 24 to 36 months. In cases of extensive pulmonary disease, cavitary lesions, or treatment failure, surgical resection may be considered as additional therapy to antibiotics.

References

Levendosky, Keith, et al. “Comprehensive Essentiality Analysis of the Mycobacterium Kansasii Genome by Saturation Transposon Mutagenesis and Deep Sequencing.” mBio, vol. 14, no. 4, pp. e00573-23. PubMed Central, https://doi.org/10.1128/mbio.00573-23. Accessed 18 Apr. 2024.

Luo, Tao, et al. “Population Genomics Provides Insights into the Evolution and Adaptation to Humans of the Waterborne Pathogen Mycobacterium Kansasii.” Nature Communications, vol. 12, no. 1, May 2021, p. 2491. www.nature.com, https://doi.org/10.1038/s41467-021-22760-6.

“Mycobacterium Kansasii.” Mycobacterium Kansasii - an Overview | ScienceDirect Topics,www.sciencedirect.com/topics/immunology-and microbiology/mycobacterium-kansasii. Accessed 18 Apr. 2024.

StatPearls. “Mycobacterium Kansasii Infection.” StatPearls, StatPearls Publishing, 8 Aug. 2023, www.statpearls.com/articlelibrary/viewarticle/25421/.

Author

Page authored by Cameron Phipps and Adrian Pena, students of Prof. Jay Lennon at Indiana University.