MMP-9 overexpression is associated with a poor outcome in MDR-TB patients, indicating that MMP-9 is a suitable target for MDR-TB therapy. MMP-9 also includes SNPs that occur at inhibitor binding areas as well as zinc ions. As a result of polymorphisms, the usage of MMP-9 inhibitors for MDR-TB might vary. Through molecular simulation, it has been found that the mutant MMP-9 has a larger cavity and a more lipophilic surface. The docking tests revealed that EGTA had the least amount of binding energy to both wild-type and mutant MMP-9. The wildtype MMP-9 can bind zinc when EGTA is in the active site. This shows that using EGTA to chelate Zn is only partially successful. However, the binding energy of EGTA at the active site suggests that it may be a competitor to MMP-9 substrates. On the other hand, Zn is not involved in the interaction of the mutant MMP-9-EGTA complex.

Matrix metalloproteinases (MMPs) are proteins that play a role in the inflammatory and remodeling processes caused by infections, including pulmonary tuberculosis (TB), especially multidrug resistance. This study aims to correlate the relationship between serum levels and polymorphism of MMP-1 and MMP-9 with cavity characteristics, such as number, diameter, wall thickness as well as distribution of fibrosis in Multidrug-Resistant (MDR)- and Drug-Sensitive (DS)-TB patients. This study used a comparative cross-sectional study design. The subjects came from outpatients at Abdoel Moelok Hospital, Lampung Indonesia had passed the ethical test. Subjects were divided into two groups, 34 subjects in the MDR-TB group and 36 subjects in the DS-TB group. The levels of MMP-1 and MMP-9 were carried out by ELISA test, genotype of MMP-1 and MMP-9 were determined using PCR-Sequencing method. In addition, cavities and fibrosis were measured using thoracic High-Resolution Computerized Tomography (HRCT) imaging. There was significant difference in the number of cavities more than 6, 6 mm in diameter, as well as cavity thickness in MDR-TB compared to DS-TB patients. Fibrosis distribution in lung segments was also different significantly in MDR-TB compared to DS-TB. Although MMP-9 levels in the MDR-TB group were highest than in the DS-TB group, there was no statistically significant. This study showed that there was a correlation between MDR-TB and DS-TB regarding the number of cavities, cavity diameter, cavity wall thickness, and distribution of fibrosis in the affected lung segments as measured by HRCT. There was no correlation between MMP-1 (-1607G) and MMP-9 (C1562T) genotypes and MMP-1 and MMP-9 serum levels, the MMP‑1 genotype in the two study groups differed significantly and was a risk factor for five times the incidence of MDR-TB. In addition, there was a substantial difference in cavity wall thickness between the G/G MMP-1 1607 genotype and the T/T MMP-9 genotype in the two study groups.