Tuberculosis remains a severe worldwide health threat. A thorough understanding of Mycobacterium tuberculosis pathogenesis will facilitate the development of new treatments for tuberculosis. Numerous bacterial pathogens possess specialized protein secretion systems that are dedicated to the export of virulence factors. Mycobacterium tuberculosis is part of a developing group of pathogenic bacteria that share the uncommon property of possessing two secA genes (secA1 and secA2). In mycobacteria, SecA1 is the essential 'housekeeping' SecA protein whereas SecA2 is an accessory secretion factor. Here we demonstrate that SecA2 contributes to the pathogenesis of M. tuberculosis. A deletion of the secA2 gene in M. tuberculosis attenuates the virulence of the organism in mice. By comparing the profile of proteins secreted by wild-type M. tuberculosis and the DeltasecA2 mutant, we identified superoxide dismutase A (SodA) as a protein dependent on SecA2 for secretion. SodA lacks a classical signal sequence for protein export. Our data suggests that SecA2-dependent export is a new type of secretion pathway that is part of a virulence mechanism of M. tuberculosis to elude the oxidative attack of macrophages.

Structural analysis of compounds identified as lipid I and II fromMycobacterium smegmatis demonstrated that the lipid moiety is decaprenyl phosphate; thus, M. smegmatis is the first bacterium reported to utilize a prenyl phosphate other than undecaprenyl phosphate as the lipid carrier involved in peptidoglycan synthesis. In addition, mass spectrometry showed that the muropeptides from lipid I are predominantly N-acetylmuramyl-L-alanine-D-glutamate-meso-diaminopimelic acid-D-alanyl-D-alanine, whereas those isolated from lipid II form an unexpectedly complex mixture in which the muramyl residue and the pentapeptide are modified singly and in combination. The muramyl residue is present as N-acetylmuramic acid, N-glycolylmuramic acid, and muramic acid. The carboxylic functions of the peptide side-chains of lipid II showed three types of modification, with the dominant one being amidation. The preferred site for amidation is the free carboxyl group of the meso-diaminopimelic acid residue. Diamidated species were also observed. The carboxylic function of the terminal D-alanine of some molecules is methylated, as are all three carboxylic acid functions of other molecules. This study represents the first structural analysis of mycobacterial lipid I and II and the first report of extensive modifications of these molecules. The observation that lipid I was unmodified strongly suggests that the lipid II intermediates of M. smegmatis are substrates for a variety of enzymes that introduce modifications to the sugar and amino acid residues prior to the synthesis of peptidoglycan.Peptidoglycans are essential components of bacterial cell walls, providing both mechanical strength and shape. The basic structure of peptidoglycan is common among most of the eubacteria, consisting of glycan chains composed of alternating units of ␤134-linked N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc). The lactyl group of the MurNAc residue usually carries a short peptide (L-Ala-DGlu-meso-diaminopimelic acid [DAP]-D-Ala-D-Ala) that forms bonds with the peptide side chains of neighboring glycan strands, thus providing mechanical strength (35). Although the basic structure of peptidoglycan remains the same among eubacterial species, there are significant variations (16, 29). The structure of the mycobacterial peptidoglycan is an example of such divergence (16,27,40). The glycan chains of mycobacterial peptidoglycan are composed of alternating units of ␤134-linked GlcNAc and N-glycolylmuramic acid (MurNGlyc) in which the N-acetyl function has been oxidized to an N-glycolyl function. The carbon-6 position of some of the muramic acid residues forms a phosphodiester bond with the ␣-L-rhamnopyranose-(133)-␣-D-GlcNAc(1-P) linker region of the galactan chain of the arabinogalactan (24), and about a third of the peptide cross bridges occur between the carboxyl group of the L-center of one DAP residue and the amino group of the D-center of another DAP residue, forming a L,D-cross-link (40); the rest of the cross-links are between the carbo...

It appears that the risk of dyspepsia, constipation, and GERD are higher among those who have AGE during a confirmed norovirus outbreak. Although these findings need confirmation, they suggest that dysmotility may result subsequent to these infections. If confirmed, the costs and morbidity associated with the chronic consequences of norovirus should be considered.

Brucellosis is an important public health problem in Peru. We evaluated 48 human Brucella melitensis biotype 1 strains from Peru between 2000 and 2006. MICs of isolates to doxycycline, azithromycin, gentamicin, rifampin, ciprofloxacin, and trimethoprim-sulfamethoxazole were determined by the Etest method. All isolates were sensitive to tested drugs during the periods of testing. Relapses did not appear to be related to drug resistance.

The lysis centrifugation technique is preferred for culturing Brucella spp. at all stages of brucellosis because it yields 25% more positive results and on average provides results 10 days earlier than the Ruiz-Castaneda method. This lysis method is inexpensive and easier to use and may be used in laboratories with limited expertise or equipment if all safety precautions are taken.