Mycobacterium kansasii has emerged as an important nontuberculous mycobacterium pathogen, whose incidence and prevalence have been increasing in the last decade. M. kansasii can cause pulmonary tuberculosis clinically and radiographically indistinguishable from that caused by Mycobacterium tuberculosis infection. Unlike the widely-studied M. tuberculosis, little is known about the innate immune response against M. kansasii infection. Although inflammasome activation plays an important role in host defense against bacterial infection, its role against atypical mycobacteria remains poorly understood. In this report, the role of inflammasome activity in THP-1 macrophages against M. kansasii infection was studied. Results indicated that viable, but not heat-killed, M. kansasii induced caspase-1-dependent IL-1β secretion in macrophages. The underlying mechanism was found to be through activation of an inflammasome containing the NLR (Nod-like receptor) family member NLRP3 and the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD). Further, potassium efflux, lysosomal acidification, ROS production and cathepsin B release played a role in M. kansasii-induced inflammasome activation. Finally, the secreted IL-1β derived from caspase-1 activation was shown to restrict intracellular M. kansasii. These findings demonstrate a biological role for the NLRP3 inflammasome in host defense against M. kansasii.

Ganoderma lucidum (G. lucidum) is a medicinal mushroom long used in Asia as a folk remedy to promote health and longevity. Recent studies indicate that G. lucidum activates NK cells, but the molecular mechanism underlying this effect has not been studied so far. To address this question, we prepared a water extract of G. lucidum and examined its effect on NK cells. We observed that G. lucidum treatment increases NK cell cytotoxicity by stimulating secretion of perforin and granulysin. The mechanism of activation involves an increased expression of NKG2D and natural cytotoxicity receptors (NCRs), as well as increased phosphorylation of intracellular MAPKs. Our results indicate that G. lucidum induces NK cell cytotoxicity against various cancer cell lines by activating NKG2D/NCR receptors and MAPK signaling pathways, which together culminate in exocytosis of perforin and granulysin. These observations provide a cellular and molecular mechanism to account for the reported anticancer effects of G. lucidum extracts in humans.

bSubinhibitory doses of antibiotics have been shown to cause changes in bacterial morphology, adherence ability, and resistance to antibiotics. In this study, the effects of subinhibitory doses of aminoglycoside antibiotics on Mycobacterium abscessus were investigated. The treatment of M. abscessus cells with subinhibitory doses of amikacin was found to change their colony from a smooth to a rough morphotype and increase their ability to adhere to a polyvinylchloride plate, aggregate in culture, and resist phagocytosis and killing by macrophages. M. abscessus cells treated with a subinhibitory dose of amikacin also became more potent in Toll-like receptor 2 (TLR-2) stimulation, leading to increased tumor necrosis factor alpha (TNF-␣) production by macrophages. The MAB_3508c gene was shown to play a role in mediating these phenotypic changes, as its expression in M. abscessus cells was increased when they were treated with a subinhibitory dose of amikacin. In addition, overexpression of MAB_3508c in M. abscessus cells caused changes similar to those induced by subinhibitory doses of amikacin, including a switch from smooth to rough colony morphology, increased ability to aggregate in liquid culture, decreased motility, and increased resistance to killing by macrophages. These findings suggest the importance of using sufficient doses of antibiotics for the treatment of M. abscessus infections.A ntibiotics have been widely used to treat infectious diseases. However, at subinhibitory concentrations, antibiotics may act as signal molecules and modulate bacterial phenotypes such as virulence, colony morphology, and biofilm formation (1, 2). Transcriptomic and proteomic analyses reveal that subinhibitory doses of antibiotics can cause significant changes in gene expression profiles in Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa (1,(3)(4)(5).Mycobacterium abscessus is a rapid-growing nontuberculosis mycobacterium. It is a common cause of infections in patients after tympanostomy tube placement and in those with surgical wounds or cystic fibrosis (6-10). Prolonged antibiotic therapy is generally required for treatment of infections caused by M. abscessus because of its intrinsic and acquired resistance to multiple antibiotics. Commonly used antibiotics for M. abscessus infections include clarithromycin, cefoxitin, tigecycline, and amikacin (AMK) (11).Amikacin is an aminoglycoside and is the most effective bactericidal antibiotic for M. abscessus. We have found that subinhibitory doses of amikacin can convert colonies of M. abscessus from a smooth to a rough morphotype. Because colony morphology is related to virulence, we investigated the effects of subinhibitory doses of amikacin on various activities of M. abscessus. MATERIALS AND METHODSBacteria and culture media. The M. abscessus cs1c-S strain used in this study is an attenuated variant derived from the clinical isolate cs1c-R (12). M. abscessus cells were grown at 37°C on Middlebrook 7H11 (Difco, USA) agar plates supplement...

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