Infectious diseases caused by clinically important Mycobacteria continue to be an important public health problem worldwide primarily due to emergence of drug resistance crisis. In recent years, the control of tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (MTB), is hampered by the emergence of multidrug resistance (MDR), defined as resistance to at least isoniazid (INH) and rifampicin (RIF), two key drugs in the treatment of the disease. Despite the availability of curative anti-TB therapy, inappropriate and inadequate treatment has allowed MTB to acquire resistance to the most important anti-TB drugs. Likewise, for most mycobacteria other than MTB, the outcome of drug treatment is poor and is likely related to the high levels of antibiotic resistance. Thus, a better knowledge of the underlying mechanisms of drug resistance in mycobacteria could aid not only to select the best therapeutic options but also to develop novel drugs that can overwhelm the existing resistance mechanisms. In this article, we review the distinctive mechanisms of antibiotic resistance in mycobacteria.

Colistin is one of the last-resort therapeutic agents to combat multidrug-resistant Gram-negative bacteria (GNB) including Klebsiella pneumoniae. Although it happens rarely, resistance to colistin has been reported for several GNB. A total of 20 colistin resistant (col-R) and three colistin susceptible (col-S) clinical isolates of K. pneumoniae were studied to explore the underlying mechanisms of colistin resistance. The presence of plasmid encoded resistance genes, mcr-1, mcr-2, mcr-3, and mcr-4 genes were examined by PCR. The nucleotide sequences of pmrA, pmrB, phoP, phoQ, and mgrB genes were determined. To evaluate the association between colistin resistance and upregulation of pmrHFIJKLM and pmrCAB operons, transcriptional level of the pmrK and pmrC genes encoding for lipopolysaccharide target modifying enzymes was quantified by RT-qPCR analysis. None of the plasmid encoded resistance genes were detected in the studied isolates. Inactivation of MgrB due to nonsense mutations and insertion of IS elements was observed in 15 col-R isolates (75%). IS elements (IS5-like and IS1-like families) most commonly targeted the coding region and in one case the promoter region of the mgrB. Complementation with wild-type MgrB restored colistin susceptibility in isolates with altered mgrB. All col-R isolates lacked any genetic alterations in the pmrA, phoP, and phoQ genes and substitutions identified in the pmrB were not found to be involved in resistance conferring determined by complementation assay. Colistin resistance linked with upregulation of pmrHFIJKLM and pmrCAB operons with the pmrK and pmrC being overexpressed in 20 and 11 col-R isolates, respectively. Our results demonstrated that MgrB alterations are the major mechanisms contributing to colistin resistance in the tested K. pneumoniae isolates from Iran.

Oxacillin resistance was present in 99 of 277 (36%) consecutive Staphylococcus aureus isolates collected from hospital patients in Tehran during a 15-month period (January 2004-March 2005). The majority of isolates (77/99 = 78%) had been cultured from wounds or blood. The staphylococcal cassette chromosome mec (SCCmec) types and antimicrobial susceptibility patterns of 99 methicillin-resistant S. aureus (MRSA) strains were determined. Disk diffusion and agar dilution methods were used to determine the susceptibility of isolates to antimicrobial agents as instructed by Clinical and Laboratory Standards Institute. The presence of mecA and SCCmec types was determined by PCR and multiplex PCR. All MRSA isolates were susceptible to vancomycin (MIC90