M. tuberculosis grows slowly (i.e., it has a doubling time of 18 hours, in contrast to most bacteria, which can double in number in 1 hour or less). Because growth is so slow, cultures of clinical specimens must be held for 6 to 8 weeks before being recorded as negative. M. tuberculosis can be cultured on bacteriologic media, whereas M. leprae cannot. Media used for its growth (e.g., Löwenstein-Jensen medium) contain complex nutrients (e.g., egg yolk) and dyes (e.g., malachite green). The dyes inhibit the unwanted normal flora present in sputum samples.
M. tuberculosis is an obligate aerobe; this explains its predilection for causing disease in highly oxygenated tissues such as the upper lobe of the lung and the kidney. The acid-fast property of M. tuberculosis (and other mycobacteria) is attributed to long-chain (C78–C90) fatty acids called mycolic acids in the cell wall.
Cord factor (trehalose dimycolate) is correlated with virulence of the organism. Virulent strains grow in a characteristic “serpentine” cordlike pattern, whereas avirulent strains do not. The organism also contains several proteins, which, when combined with waxes, elicit delayed hypersensitivity. These proteins are the antigens in the purified protein derivative (PPD) skin test (also known as the tuberculin skin test). A lipid located in the bacterial cell wall called phthiocerol dimycocerosate is required for pathogenesis in the lung.
M. tuberculosis is relatively resistant to acids and alkalis. NaOH is used to concentrate clinical specimens; it destroys unwanted bacteria, human cells, and mucus but not the organ ism. M. tuberculosis is resistant to dehydration and therefore survives in dried expectorated sputum; this property may be important in its transmission by aerosol.
Strains of M. tuberculosis resistant to the main antimycobacterial drug, isoniazid (isonicotinic acid hydrazide, INH), as well as strains resistant to multiple antibiotics (called multidrug resistant or MDR strains), have become a worldwide problem. This resistance is attributed to one or more chromosomal mutations because no plasmids have been found in this organism. One of these mutations is in a gene for mycolic acid synthesis, and another is in a gene for catalase-peroxidase, an enzyme required to activate INH within the bacterium. Resistance to rifampin is caused by mutations in the gene encoding the RNA polymerase of the organism.
