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is a global pathogen of significant medical importance. A key aspect of its life cycle is the ability to enter into an altered physiological state of nonreplicating persistence during latency and resist elimination by the host immune system. One mechanism by which facilitates its survival during latency is by producing and metabolizing intracytoplasmic lipid droplets (LDs). LDs are quasi-organelles consisting of a neutral lipid core such as triacylglycerol surrounded by a phospholipid monolayer and proteins. We previously reported that PspA (phage shock protein A) associates with LDs produced in In particular, the loss or overproduction of PspA alters LD homeostasis in and attenuates the survival of during nonreplicating persistence. Here, PspA (PspA) and a Δ mutant were used as model systems to investigate the mechanism by which PspA associates with LDs and determine if other proteins associate with LDs using a mechanism similar to that for PspA. Through this work, we established that the amphipathic helix present in the first α-helical domain (H1) of PspA is both necessary and sufficient for the targeting of this protein to LDs. Furthermore, we identified other proteins that also possess amphipathic helices similar to PspA H1, including a subset that localize to LDs. Altogether, our results indicate that amphipathic helices may be an important mechanism by which proteins target LDs in prokaryotes. spp. are one of the few prokaryotes known to produce lipid droplets (LDs), and their production has been linked to aspects of persistent infection by Unfortunately, little is known about LD production in these organisms, including how LDs are formed, their function, or the identity of proteins that associate with them. In this study, an established LD protein and a surrogate host were used as model systems to study the interactions between proteins and LDs in bacteria. Through these studies, we identified a commonly occurring protein motif that is able to facilitate the association of proteins to LDs in prokaryotes.

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), remains a significant cause of morbidity and mortality worldwide, despite the availability of a live attenuated vaccine and anti-TB antibiotics. The vast majority of individuals infected with M. tuberculosis develop an asymptomatic latent infection in which the bacterium survives within host-generated granulomatous lesions in a physiologically altered metabolic state of nonreplicating persistence. The granuloma represents an adverse environment, as M. tuberculosis is exposed to various stressors capable of disrupting the essential constituents of the bacterium. In Gram-negative and Gram-positive bacteria, resistance to cell envelope stressors that perturb the plasma membrane is mediated in part by proteins comprising the phage shock protein (Psp) system. PspA is an important component of the Psp system; in the presence of envelope stress, PspA localizes to the inner face of the plasma membrane, homo-oligomerizes to form a large scaffold-like complex, and helps maintain plasma membrane integrity to prevent a loss of proton motive force. M. tuberculosis and other members of the Mycobacterium genus are thought to encode a minimal functional unit of the Psp system, including an ortholog of PspA. Here, we show that Rv2744c possesses structural and physical characteristics that are consistent with its designation as a PspA family member. However, although Rv2744c is upregulated under conditions of cell envelope stress, loss of Mycobacterium tuberculosis is the causative agent of the respiratory disease tuberculosis (TB) and is a human-specific pathogen of global importance. This bacterium is responsible for Ͼ9.6 million new cases of TB and 1.5 million deaths annually (1), ranking TB as the leading cause of death in the world due to an infectious agent, alongside HIV/AIDS. A key aspect of the M. tuberculosis life cycle is its ability to establish asymptomatic latent infections and reactivate to cause active disease and transmission to new hosts (reviewed in reference 2). During latency, M. tuberculosis exists in a state of nonreplicating persistence (NRP), a poorly understood physiological state in which the bacterium can utilize alternative carbon sources and energy-generating pathways for long-term survival within the host (3-6). While a live attenuated vaccine for TB is available (Mycobacterium bovis bacillus Calmette-Guérin [BCG]), its efficacy at preventing adult pulmonary TB and thus M. tuberculosis retransmission is highly varied (7,8). Furthermore, M. tuberculosis exhibits increased phenotypic resistance to anti-TB antibiotics during NRP (2, 9), making it more difficult to kill this organism in latently infected individuals. Therefore, new strategies and/or therapeutics are urgently needed to help eradicate TB. This will require an improved understanding of the mechanisms utilized by M. tuberculosis to persist and/or reactivate within the host.

These data suggest that fs289X is a null mutation, rendering the patients with the compound heterozygous genotype of fs289X/P932L to exclusively express P932L homomeric channels that may have caused the "dystrophic" phenotype.

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A 45-year-old woman was diagnosed as having the unclassified form of botulism. Her intestines may have been predisposed to colonization with Clostridium botulinum because of a jejunoileal bypass procedure that had been done several years earlier. One other similar case has been reported.

Evaluation of insulin sensitivity in 12 patients with myotonic dystrophy gave results different from those found in other insulin-resistant conditions. Nine of our subjects were insensitive to exogenous insulin, but only three had elevated fasting insulin concentrations. Eight had an excessive insulin response to a glucose challenge. Monocyte insulin receptor affinity was decreased (myotonics, 1.21 +/- 0.74 X 10(9) liters per mole; controls, 2.62 +/- 1.28 X 10(9)), and this parameter correlated best with the insulin resistance. No circulating receptor antibody or insulin binding inhibitor was found. Our studies suggest that the insulin resistance seen in patients with myotonic dystrophy is related to decreased insulin receptor affinity.