Humans are the only known reservoirs of<unk> . A misconception is that<unk>  can be spread by shaking hands, making contact with toilet seats, sharing food or drink, or sharing toothbrushes. However, major spread is through air droplets originating from a person who has the disease either coughing, sneezing, speaking, or singing. When in the lungs,<unk>  is phagocytosed by alveolar macrophages, but they are unable to kill and digest the bacterium. Its cell wall inhibits the fusion of the phagosome with the lysosome, which contains a host of antibacterial factors. Specifically,<unk>  blocks the bridging molecule, early endosomal autoantigen 1 (EEA1); however, this blockade does not prevent fusion of vesicles filled with nutrients. In addition, production of the diterpene isotuberculosinol prevents maturation of the phagosome. The bacteria also evades macrophage-killing by neutralizing reactive nitrogen intermediates. More recently,<unk>  has been shown to secrete and cover itself in 1-tuberculosinyladenosine (1-TbAd), a special nucleoside that acts as an antacid, allowing it to neutralize pH and induce swelling in lysosomes. In<unk>  infections, PPM1A levels were found to be upregulated, and this, in turn, would impact the normal apoptotic response of macrophages to clear pathogens, as PPM1A is involved in the intrinsic and extrinsic apoptotic pathways. Hence, when PPM1A levels were increased, the expression of it inhibits the two apoptotic pathways. With kinome analysis, the JNK/AP-1 signalling pathway was found to be a downstream effector that PPM1A has a part to play in, and the apoptotic pathway in macrophages are controlled in this manner. As a result of having apoptosis being suppressed, it provides<unk>  with a safe replicative niche, and so the bacteria are able to maintain a latent state for a prolonged time. Granulomas, organized aggregates of immune cells, are a hallmark feature of<unk>  infection. Granulomas play dual roles during infection: they regulate the immune response and minimize tissue damage, but also can aid in the expansion of infection. The ability to construct<unk>  mutants and test individual gene products for specific functions has significantly advanced the understanding of its pathogenesis and virulence factors. Many secreted and exported proteins are known to be important in pathogenesis. For example, one such virulence factor is cord factor (trehalose dimycolate), which serves to increase survival within its host. Resistant strains of<unk>  have developed resistance to more than one TB drug, due to mutations in their genes. In addition, pre-existing first-line TB drugs such as rifampicin and streptomycin have decreased efficiency in clearing intracellular<unk>  due not being able to effectively penetrate the macrophage niche JNK plays a key role in the control of apoptotic pathways—intrinsic and extrinsic. In addition, it is also found to be a substrate of PPM1A activity, hence the phosphorylation of JNK would cause apoptosis to occur. Since PPM1A levels are elevated during<unk>  infections, by inhibiting the PPM1A signalling pathways, it could potentially be a therapeutic method to kill<unk> -infected macrophages by restoring its normal apoptotic function in defence of pathogens. By targeting the PPM1A-JNK signalling axis pathway, then, it could eliminate<unk> -infected macrophages. The ability to restore macrophage apoptosis to<unk> -infected ones could improve the current<unk>  chemotherapy treatment, as TB drugs can gain better access to the bacteria in the niche. thus decreasing the treatment times for<unk>  infections. Symptoms of<unk>  include coughing that lasts for more than three weeks, hemoptysis, chest pain when breathing or coughing, weight loss, fatigue, fever, night sweats, chills, and loss of appetite.<unk>  also has the potential of spreading to other parts of the body. This can cause blood in urine if the kidneys are affected, and back pain if the spine is affected. Strain variation Typing of strains is useful in the investigation of<unk>  outbreaks, because it gives the investigator evidence for or against transmission from person to person. Consider the situation where person A has<unk>  and believes he acquired it from person B. If the bacteria isolated from each person belong to different types, then transmission from B to A is definitively disproven; however, if the bacteria are the same strain, then this supports (but does not definitively prove) the hypothesis that B infected A. Until the early 2000s,<unk>  strains were typed by pulsed field gel electrophoresis. This has now been superseded by variable numbers of tandem repeats (VNTR), which is technically easier to perform and allows better discrimination between strains. This method makes use of the presence of repeated DNA sequences within the<unk>  genome. Three generations of VNTR typing for<unk>  are noted. The first scheme, called exact tandem repeat, used only five loci, but the resolution afforded by these five loci was not as good as PFGE. The second scheme, called mycobacterial interspersed repetitive unit, had discrimination as good as PFGE. The third generation (mycobacterial interspersed repetitive unit – 2) added a further nine loci to bring the total to 24. This provides a degree of resolution greater than PFGE and is currently the standard for typing<unk> . However, with regard to archaeological remains, additional evidence may be required because of possible contamination from related soil bacteria. Antibiotic resistance in<unk>  typically occurs due to either the accumulation of mutations in the genes targeted by the antibiotic or a change in titration of the drug.<unk>  is considered to be multidrug-resistant (MDR TB) if it has developed drug resistance to both rifampicin and isoniazid, which are the most important antibiotics used in treatment. Additionally, extensively drug-resistant<unk>  (XDR TB) is characterized by resistance to both isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin).<unk>  (stained red) in tissue (blue) Cording<unk>  (H37Rv strain) culture on the luminescent microscopy
Mycobacterium tuberculosis
Mycobacterium kansasii
Mycoplasma pneumonia
Bacillus anthracis
Mycoplasma
Pneumocystis jirovecii
Mycobacterium avium complex
Cryptococcus neoformans