Impact of MBL-2 coding region polymorphism on modulation of HAND and HIV-1 acquisition.

BACKGROUND: Mannose-binding lectin 2 (MBL2) gene has a significant role in the essential protective mechanism of the body. Variations reported in the genetic makeup of this gene influence the circulating MBL levels that could lead to the vulnerability to various viral infections including HIV. Hence, we assessed the MBL2 coding region (52A/D, 54A/B, and 57A/C) variations in HIV-associated neurocognitive disorders (HAND). METHOD: In this proposed study, 208 HIV seropositive individuals were included, 104 were on ART undergone for IHDS evaluation (44 HAND+60 without HAND), and 104 HIV seropositive individuals naïve to ART, and 130 unrelated HIV uninfected individuals. PCR-RFLP was used to genotype the MBL2 coding region polymorphism (52A/D, 54A/B and 57A/C). RESULTS: MBL-2 57AC genotype was associated with risk of HAND severity (OR = 4.69, P = 0.0009). MBL-2 57AC and 57C alleles were associated with susceptibility to HAND (OR = 3.14, P = 0.003). Furthermore, the MBL-2 57AC genotype and 57C allele were found to be significantly linked with the susceptibility to HIV disease severity. (OR = 6.34, P = 0.001; 16.82% vs. 3.46%, OR = 5.64, P = 0.001). Haplotype ACA was significantly linked with susceptibility to HAND and its severity (OR = 3.23, P = 0.004, 26.1%-8.1%, OR = 4.70, P = 0.0024), similarly, haplotype ACA was linked with the acquisition of HIV-1 (OR = 4.26, P = 0.005). MBL-2 57AC genotype in presence of tobacco showed a significantly higher risk for HIV disease severity (48.0% vs. 12.5%, OR = 7.00, P = 0.035). Alcohol-taking HIV seropositive individuals on ART showed a greater MBL-2 57AC genotype than with alcohol-taking naïve to ART (32.3% vs. 15.4%, OR = 2.75, P = 0.40). CONCLUSION: MBL-2 57AC genotype and haplotype ACA were associated with the modulation of HAND. Individuals with haplotype ACA were at higher risk of HIV-1 acquisition.

Issues with the current drugs for Mycobacterium tuberculosis cure and potential of cell envelope proteins for new drug discovery.

Mycobacterium tuberculosis has been the smartest pathogen ever and a challenge to drug development. Its replicative machinery is unique, so targeting the same for killing the pathogen remains a challenge. Our body typically throws out the drugs before they see the bacterium multiply. The pathogen has also learned how to remove drugs from its internal chambers and not allow them to reach their targets. Another strategy for Mtb is the mutation of the targets to reject drug binding and bypass the drug's inhibitory actions. In this review, we tried to explore possible targets on the outer side of the bacterial cell. We have also explored if those targets are promising enough and if there are drugs or inhibitors available. We also discuss the essential proteins and why they remain to be a good target. We concluded that the cell envelope has got a few proteins that can be targeted in isolation or maybe along with other machinery while making the outer environment more conducive for penetration of current drugs or newly proposed drugs.