Investing in success: student experiences in a structured, decelerated preclinical medical school curriculum.

Purpose: Many students in the Michigan State University College of Human Medicine (CHM) are non-traditional with unique needs and experiences. To meet these needs, in 1988 CHM developed a structured Extended Curriculum Program (ECP), which allows students to take longer than 2 years to complete the preclinical curriculum. This work examined the reasons why students extended their programs, their perceptions of that experience, and the outcome with respect to satisfaction and success in their careers after graduation.

A Moonlighting Enolase from Lactobacillus gasseri does not Require Enzymatic Activity to Inhibit Neisseria gonorrhoeae Adherence to Epithelial Cells.

Enolases are generally thought of as cytoplasmic enzymes involved in glycolysis and gluconeogenesis. However, several bacteria have active forms of enolase associated with the cell surface and these proteins are utilized for functions other than central metabolism. Recently, a surface-associated protein produced by Lactobacillus gasseri ATCC 33323 with homology to enolase was found to inhibit the adherence of the sexually transmitted pathogen, Neisseria gonorrhoeae, to epithelial cells in culture.

Crystal structure of an efficacious gonococcal adherence inhibitor: an enolase from Lactobacillus gasseri.

Enolases are highly conserved metalloenzymes ubiquitous to cellular metabolism. While these enzymes share a large degree of sequence and structural similarity, they have been shown to possess a wide range of moonlighting functions. Recent studies showed that an enolase from Lactobacillus gasseri impedes the ability of Neisseria gonorrhoeae to adhere to epithelial cells.

Expression of a Clostridium perfringens type IV pilin by Neisseria gonorrhoeae mediates adherence to muscle cells.

Clostridium perfringens is an anaerobic, Gram-positive bacterium that causes a range of diseases in humans, including lethal gas gangrene. We have recently shown that strains of C. perfringens move across the surface of agar plates by a unique type IV pilus (TFP)-mediated social motility that had not been previously described.

Lactobacilli at the front line of defense against vaginally acquired infections.

Probiotics are microorganisms that provide a health benefit to the host and are promoted as alternatives for the treatment and prevention of infectious diseases and other conditions. One of the most rapidly developing areas of probiotic research is in the management of vaginally acquired infections. Several Lactobacillus species produce compounds that kill or inhibit the growth of vaginally acquired pathogens.

Expression, purification, crystallization and preliminary X-ray studies of Lactobacillus jensenii enolase.

Recombinant Lactobacillus jensenii enolase fused to a C-terminal noncleavable His tag was expressed in Escherichia coli, purified and crystallized by sitting-drop vapor diffusion. A complete data set was collected to 3.25 A resolution.

Lactobacillus jensenii surface-associated proteins inhibit Neisseria gonorrhoeae adherence to epithelial cells.

High numbers of lactobacilli in the vaginal tract have been correlated with a decreased risk of infection by the sexually transmitted pathogen Neisseria gonorrhoeae. We have previously shown that Lactobacillus jensenii, one of the most prevalent microorganisms in the healthy human vaginal tract, can inhibit gonococcal adherence to epithelial cells in culture. Here we examined the role of the epithelial cells and the components of L.

Increased expression of the type IV secretion system in piliated Neisseria gonorrhoeae variants.

Neisseria gonorrhoeae produces a type IV secretion system that secretes chromosomal DNA. The secreted DNA is active in the transformation of other gonococci in the population and may act to transfer antibiotic resistance genes and variant alleles for surface antigens, as well as other genes. We observed that gonococcal variants that produced type IV pili secreted more DNA than variants that were nonpiliated, suggesting that the process may be regulated.

Attenuated enzootic (pestoides) isolates of Yersinia pestis express active aspartase.

It is established that Yersinia pestis, the causative agent of bubonic plague, recently evolved from enteropathogenic Yersinia pseudotuberculosis by undergoing chromosomal degeneration while acquiring two unique plasmids that facilitate tissue invasion (pPCP) and dissemination by fleabite (pMT). Thereafter, plague bacilli spread from central Asia to sylvatic foci throughout the world. These epidemic isolates exhibit a broad host range including man as opposed to enzootic (pestoides) variants that remain in ancient reservoirs where infection is limited to muroid rodents.

Midpregnancy vaginal fluid defensins, bacterial vaginosis, and risk of preterm delivery.

Objective: To assess relations among midpregnancy vaginal defensin levels, a component of the host innate immune response, bacterial vaginosis, and risk of preterm delivery. These relations are compared across race groups because previous studies have repeatedly shown that the prevalence of bacterial vaginosis and the risk of preterm delivery are greater in African-American women compared with that in white women.

Methods: Data are from a prospective study that enrolled pregnant women from 52 clinics in five Michigan communities.

A missense mutation causes aspartase deficiency in Yersinia pestis.

It is established that cells of Yersinia pestis, the causative agent of bubonic plague, excrete l-aspartic acid at the expense of exogenous l-glutamic acid during expression of the low-calcium response. Results of enzymic analysis provided here suggest that a previously defined deficiency of aspartase (AspA) accounts for this phenomenon rather than an elevated oxaloacetate pool. The only known distinction between most sequenced isolates of aspA from Y.

Inhibition of Neisseria gonorrhoeae epithelial cell interactions by vaginal Lactobacillus species.

High levels of Lactobacillus, the dominant genus of the healthy human vaginal microbiota, have been epidemiologically linked to a reduced risk of infection following exposure to the sexually transmitted pathogen Neisseria gonorrhoeae. In this work, a cell culture model of gonococcal infection was adapted to examine the effects of lactobacilli on gonococcal interactions with endometrial epithelial cells in vitro. Precolonization of epithelial cells with Lactobacillus jensenii, Lactobacillus gasseri ATCC 33323, or L.

Two ABC transporter operons and the antimicrobial resistance gene mtrF are pilT responsive in Neisseria gonorrhoeae.

Retraction of type IV pili is mediated by PilT. We show that loss of pilT function leads to upregulation of mtrF (multiple transferable resistance) and two operons encoding putative ABC transporters in Neisseria gonorrhoeae MS11. This effect occurs indirectly through the transcriptional regulator FarR, which until now has been shown to regulate only farAB.

RpoH mediates the expression of some, but not all, genes induced in Neisseria gonorrhoeae adherent to epithelial cells.

Neisseria gonorrhoeae (gonococcus [GC]), is highly adapted to the human host, the only known reservoir for gonococcal infection. However, since it is sexually transmitted, infection of a new host likely requires a regulatory response on the part of the gonococcus to respond to this significant change in environment. We previously showed that adherence of gonococci to epithelial cells results in changes of gene expression in the bacteria that presumably prepare them for subsequent steps in the infection process.

Expression capable library for studies of Neisseria gonorrhoeae, version 1.0.

Background: The sexually transmitted disease, gonorrhea, is a serious health problem in developed as well as in developing countries, for which treatment continues to be a challenge. The recent completion of the genome sequence of the causative agent, Neisseria gonorrhoeae, opens up an entirely new set of approaches for studying this organism and the diseases it causes. Here, we describe the initial phases of the construction of an expression-capable clone set representing the protein-coding ORFs of the gonococcal genome using a recombination-based cloning system.

Global gene expression and the role of sigma factors in Neisseria gonorrhoeae in interactions with epithelial cells.

Like many bacterial pathogens, Neisseria gonorrhoeae must adapt to environmental changes in order to successfully colonize and proliferate in a new host. Modulation of gene expression in response to environmental signals is an efficient mechanism used by bacteria to achieve this goal. Using DNA microarrays and a tissue culture model for gonococcal infection, we examined global changes in gene expression in N.

Purification, characterization and preliminary X-ray crystallographic studies on Neisseria gonorrhoeae Gly1ORF1.

Gly1ORF1 is a protein produced by the two pathogenic Neisseria species, N. gonorrhoeae and N. meningitidis, but not by commensal Neisseria, suggesting that it may be involved in pathogenesis.

Identification of ZipA, a signal recognition particle-dependent protein from Neisseria gonorrhoeae.

A genetic screen designed to identify proteins that utilize the signal recognition particle (SRP) for targeting in Escherichia coli was used to screen a Neisseria gonorrhoeae plasmid library. Six plasmids were identified in this screen, and each is predicted to encode one or more putative cytoplasmic membrane (CM) proteins. One of these, pSLO7, has three open reading frames (ORFs), two of which have no similarity to known proteins in GenBank other than sequences from the closely related N.

Role for both DNA and RNA in GTP hydrolysis by the Neisseria gonorrhoeae signal recognition particle receptor.

The prokaryotic signal recognition particle (SRP) targeting system is a complex of two proteins, FtsY and Ffh, and a 4.5S RNA that targets a subset of proteins to the cytoplasmic membrane cotranslationally. We previously showed that Neisseria gonorrhoeae PilA is the gonococcal FtsY homolog.