Effect of low concentrations of quinolone antibiotics on bacterial virulence mechanisms

Recent studies have shown that exposure to quinolone antibiotics at or below the minimal inhibitory concentration (MIC) results in reduction in the level of production or total elimination of certain factors that contribute to the virulence of bacteria. This study was designed to determine whether low concentrations of enoxacin, lomefloxacin, and ciprofloxacin altered the morphology or affected the production of various virulence factors in several different genera of bacteria. The factors studied were nuclease and a toxin production in Staphylococcus aureus, cell size, pili and fimbriae production, and adherence of Salmonella typhimurium, Escherichia coli, and Pseudomonas aeruginosa to urinary epithelial cells and dog bladder cells, and the major virulence factor in Yersinia pseudotuberculosis. In addition, the effect of growth in low levels of enoxacin on phagocytosis of S. aureus by human polymorphonuclear leukocytes (PMNs) was studied. Following exposure to subinhibitory levels of quinolones tested, significant reduction in activity or complete elimination was seen in all of those factors measured. Minor differences were noted in the efficiency of elimination among the three quinolones tested. At as low as 1/8 MIC there is significant enhancement of phagocytic activity by human PMNs. These data suggest that exposure to quinolones at concentrations below the MIC disrupts the regulatory mechanisms that control cell morphology, adherence as well as exocellular enzyme production and plasmid maintenance. This may mean that certain virulent organisms that survive exposure to quinolone antibiotics may be less likely to produce or maintain the disease state in susceptible hosts.     

Effect of macrolides on cytokine mRNA expression in human whole blood model

Recently, low dose and long term use of Macrolides (Mls) has been reported to be effective in treatment of chronic lower respiratory tract infections, however its mechanism is still obscure. We evaluated the effect of Mls (EM, AZM, RKM) on cytokine mRNA expressions. We preincubated the whole blood with several concentrations of Mls and removed the Mls and then stimulated human whole blood with LPS as an experimental vivo model. In order to examine cytokine mRNA expressions, we used the RT-PCR method. Cytokine mRNA expressions were suppressed significantly (p < 0.05) by pretreatment with EM, AZM; moreover, the suppression was peaked at low concentrations (0.04 approximately 0.2 microgram/ml). Although, Cytokine mRNA expressions were not suppressed by pretreatment with RKM. These results suggest that EM, AZM have suppression on Cytokine mRNA expressions, and consequently, this suppression has a reasonable effect for DPB patients.     

The effects of bacterial overgrowth and hemorrhagic shock on mucosal immunity

Impairment in systemic and mucosal immune function is noted after hemorrhagic shock (HS). Overgrowth of gut microflora is common after shock insults and may act as a reservoir for intensive care unit-acquired infections and subsequent remote organ failure. Secretory immunoglobulin A (IgA), the principle immunoglobulin in intestinal secretions, is the first line of defense of mucosal surfaces. Although HS and gut bacterial overgrowth are often temporarily related, their combined effect on IgA is unknown and served as the basis for this study. After sham or HS, self-filling blind loops (SFBL) were created to affect bacterial overgrowth. Intestinal secretions were obtained 7 days later from SFBL and jejunal segments for quantitative culture. Gut washings were also obtained and secretory IgA levels determined by enzyme-linked immunosorbent assay. Bacterial overgrowth in the SFBL was associated with significant increases in IgA levels in the sham group only. IgA levels were depressed in both jejunal and SFBL segments in the HS group. Impaired humoral mucosal defense may be important mechanistically in the development of nosocomial infections and organ failure after HS, particularly with concurrent gut bacterial overgrowth.     

The role of macrolides in Streptococcus pyogenes pharyngitis

PURPOSE: This study was undertaken to compare functional results, complications, preoperative durations of disease, and rates of dysplasia and neoplasia between older and younger chronic ulcerative colitis patients undergoing restorative proctocolectomy (RPC) with mucosectomy. METHODS: A total of 392 patients with a preoperative diagnosis of chronic ulcerative colitis underwent elective RPC with mucosection and handsewn ileoanal anastomosis. Pathologic reports were reviewed, with specific reference to findings of dysplasia or cancer. Functional results concerning the number of bowel movements per 24 hour period and the incidence of fecal soilage were obtained by direct or telephone patient interview. FINDINGS: Group I consisted of 326 patients aged 5 to 49 (mean, 30.9) years and 160 women. Group II comprised 66 patients aged 50 to 74 (mean, 56.9) years and 29 women. Duration of disease was significantly longer in the older group (6.2 vs. 15.6 years; P < 0.001). The older group had significantly higher rates of dysplasia (29/326 vs. 19/66; P < 0.0001) and malignancy (14/326 vs. 9/66; P = 0.003). Rates of complication, hospital days following RPC, and total hospital days for all causes were comparable between groups. Perfect day-time continence was observed in 81.6 percent of Group I and 80 percent of Group II patients (213/261 vs. 40/50; P = 0.79). Perfect continence during sleep was observed in 65.1 percent of Group I and 62 percent of Group II patients (170/261 vs. 31/50; P = 0.67). Mean number of bowel movements per 24 hour period for Group I was 6.3 +/- 0.2 and for Group II was 7.4 +/- 0.5. Mean difference, one movement per 24 hours, was not significant (95 percent confidence interval, -0.02 to 2.1; t = 1.95, P = 0.055). CONCLUSIONS: We conclude that patients older than 50 years are suitable candidates for RPC with mucosectomy. Functional results and complication rates are similar to those observed among younger patients. Patients older than 50 years have a significantly higher rate of concurrent dysplasia and malignant degeneration than younger patients, most probably because of a longer duration of disease. RPC with mucosal excision potentially lowers this risk by elimination of all colorectal mucosa.     

The pH of the host niche controls gene expression in and virulence of Candida albicans

Little is known of the biological attributes conferring pathogenicity on the opportunistic fungal pathogen Candida albicans. Infection by this pathogen, as for bacterial pathogens, may rely upon environmental signals within the host niche to regulate the expression of virulence determinants. To determine if C. albicans responds to the pH of the host niche, we tested the virulence of strains with mutations in either of two pH-regulated genes, PHR1 and PHR2. In vitro, PHR1 is expressed when the ambient pH is at 5.5 or higher and deletion of the gene results in growth and morphological defects at neutral to alkaline pHs. Conversely, PHR2 is expressed at an ambient pH below 5.5, and the growth and morphology of the null mutant is compromised below this pH. A PHR1 null mutant was avirulent in a mouse model of systemic infection but uncompromised in its ability to cause vaginal infection in rats. Since systemic pH is near neutrality and vaginal pH is around 4.5, the virulence phenotype paralleled the pH dependence of the in vitro phenotypes. The virulence phenotype of a PHR2 null mutant was the inverse. The mutant was virulent in a systemic-infection model but avirulent in a vaginal-infection model. Heterozygous mutants exhibited partial reductions in their pathogenic potential, suggesting a gene dosage effect. Unexpectedly, deletion of PHR2 did not prevent hyphal development in vaginal tissue, suggesting that it is not essential for hyphal development in this host niche. The results suggest that the pH of the infection site regulates the expression of genes essential to survival within that niche. This implies that the study of environmentally regulated genes may provide a rationale for understanding the pathobiology of C. albicans.     

Effect of bacterial association on virulence of Entamoeba histolytica to baby hamster kidney cell monolayers

Axenic E. histolytica trophozoite strain NIH:200 and HMI:IMSS when co-associated with aerobic bacteria Escherichia coli strain K12 and serotype 056 showed marked increase in virulence as observed by destruction of baby hamster kidney (BHK) monolayers. However, when incubated with anaerobic bacterial strains Clostridium perfringens and Bacteroides fragilis virulence remained unaltered. Further, adherence of E. histolytica to BHK monolayer was found to be mediated by N-acetyl-D-galactosamine.     

The effects of mild frustration on the expression of prejudiced attitudes.

"The present study was designed to test the proposition that frustration may increase the expression of prejudice. Sixty-four S's were given a series of attitude scales, following which all were exposed to a relatively mild, experimentally induced frustration. Immediately thereafter, alternate forms of the attitude scale were administered. Significant increases were found… [and] the results were interpreted as an instance of 'targeting' of a minority group within the general framework of the scapegoat phenomenon." 23 refs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of focal brain damage on pragmatic expression.

Five Broca's and 5 Wernicke's aphasic males (ages 37–73 yrs) described 9 triplets of pictures in each of which 1 element varied and the others remained constant. Dependent variables included probability of lexicalization vs ellipsis, pronominalization, definite and indefinite article use, pragmatic word order variations in dative structure, and use of connectors. Both groups showed pragmatic sensitivity in at least 2 of these areas suggesting that the topic-focus function per se is not impaired in these aphasias. Broca's aphasics were pragmatically sensitive in lexicalization and dative structure; Wernicke's aphasics were pragmatically sensitive in lexicalization and article use. The contribution of specific grammatical and lexical impairments to the expression of a common pragmatic motive is discussed. (French abstract) (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of stereotype activation on behavior: A review of possible mechanisms.

Considerable recent research has examined the effects that activated stereotypes have on behavior. Research on both self-stereotype activation and other-stereotype activation has tended to show that people behave in ways consistent with the stereotype (e.g., walking more slowly if the elderly stereotype is activated). Interestingly, however, the dominant account for the behavioral effects of self-stereotype activation involves a hot motivational factor (i.e., stereotype threat), whereas the dominant account for the behavioral effects of other-sterotype activation focuses on a rather cold cognitive explanation (i.e., ideomotor processes). The current review compares and contrasts the behavioral research on self- and other-stereotype activation and concludes that both motivational and cognitive explanations might account for effects in each domain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Constitutive expression of the virulence genes improves the efficiency of plant transformation by Agrobacterium

Inducible virulence (vir) genes of the Agrobacterium tumefaciens tumor-inducing (Ti) plasmid are under control of a two-component regulatory system. In response to environmental factors (phenolic compounds, sugars, pH) VirA protein phosphorylates VirG, which in turn interacts with the promoters of other vir genes, causing induction. A mutation of virG, virGN54D (which codes for a Asn-54-->Asp amino acid change in the product), causes constitutive expression of other vir genes independent of virA. We have investigated whether providing Agrobacterium with a plasmid containing virGN54D augments the efficiency of transfer of the T-DNA (transferred DNA). For both tobacco and cotton, we observed an enhancement of transformation efficiency when the inciting Agrobacterium strain carries the virGN54D mutation. We also tested whether supplying Agrobacterium with a similar plasmid containing wild-type virG affects the efficiency of T-DNA transfer. An intermediate efficiency was observed when this plasmid was employed. Using a beta-glucuronidase (GUS) reporter gene to assess transient expression of T-DNA after transfer to tobacco and maize tissues, we observed a higher frequency of GUS-expressing foci after inoculation with Agrobacterium strains carrying virGN54D than with Agrobacterium carrying the wild-type virG. Gene-transfer efficiency to maize by an octopine strain was greatly improved upon introduction of virGN54D. Multiple copies of wild-type virG were equally effective in promoting transient expression efficiency in tobacco but were virtually ineffective in maize. We propose the use of virGN54D to improve the efficiency of Agrobacterium-mediated transformation, especially for recalcitrant plant species.     

Psychological mechanisms of process-control effects.

The psychological mechanisms underlying process-control effects—the tendency to evaluate a decision-making process more favorably when given an opportunity to express one's views before the decision is made—were examined. The hypothesis was that process-control effects would disappear for the favorable component of an outcome. This pattern was confirmed in a survey of Hong Kong citizens who were affected by a new subway-fare scheme. Several critical conditions that may qualify process-control effects were also tested. For perceived procedural fairness, the belief that citizens' views were considered and that the subway authority acted in good faith were found to be critical factors. For distributive fairness and reactions to the new fare scheme, the perceived favorableness of the new fare scheme was the critical factor. Implications of these findings for theories of procedural justice are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neural mechanisms of tolerance to the effects of cocaine

Chronic use of cocaine in high doses can produce tolerance as assessed by various behavioral, neurochemical, cellular and molecular measures in specific brain regions. Tolerance to cocaine is indicated by drug discrimination and intracranial self-stimulation models, which show the development of tolerance after approximately 1 week of frequent cocaine treatment, with recovery after a similar period of cocaine abstinence. Tolerance to the reinforcing properties of cocaine depends on dose, duration and frequency of cocaine self-administered by experimental animal or human subjects. The mechanism underlying this effect may involve an absolute or relative attenuation of dopamine response to cocaine challenge after frequent or repeated treatment in the nucleus accumbens (NAc). Similarly, afferent and efferent NAc circuits exhibit reduced metabolic activity, which lasts throughout the early period of withdrawal following repeated treatment. Attenuation of immediate early gene response also occurs, which might be related to a functional desensitization of dopamine D1-like receptors. Furthermore, intracellular adaptive responses to chronic cocaine exposure induce striatal dynorphin expression decreasing the behavioral potency of subsequent drug treatment. Thus, a combination of various pharmacodynamic mechanisms and the attenuation of dopamine response induced by sufficient dose, duration and frequency of cocaine exposure ultimately invoke the transient development of tolerance to the reinforcing effects of cocaine.     

Involvement of the Haemophilus ducreyi gmhA gene product in lipooligosaccharide expression and virulence

The lipooligosaccharide (LOS) present in the outer membrane of Haemophilus ducreyi is likely a virulence factor for this sexually transmitted pathogen. An open reading frame in H. ducreyi 35000 was found to encode a predicted protein that had 87% identity with the protein product of the gmhA (isn) gene of Haemophilus influenzae. In H. influenzae type b, inactivation of the gmhA gene caused the synthesis of a significantly truncated LOS which possessed only lipid A and a single 2-keto-3-deoxyoctulosonic acid molecule (A. Preston, D. J. Maskell, A. Johnson, and E. R. Moxon, J. Bacteriol. 178:396-402, 1996). The H. ducreyi gmhA gene was able to complement a gmhA-deficient Escherichia coli strain, a result which confirmed the identity of this gene. When the gmhA gene of H. ducreyi was inactivated by insertion of a cat cartridge, the resultant H. ducreyi gmhA mutant, 35000.252, expressed a LOS that migrated much faster than wild-type LOS in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When the wild-type H. ducreyi strain and its isogenic gmhA mutant were used in the temperature-dependent rabbit model for dermal lesion production by H. ducreyi, the gmhA mutant was found to be substantially less virulent than the wild-type parent strain. The H. ducreyi gmhA gene was amplified by PCR from the H. ducreyi chromosome and cloned into the pLS88 vector. When the H. ducreyi gmhA gene was present in trans in gmhA mutant 35000.252, expression of the gmhA gene product restored the virulence of this mutant to wild-type levels. These results indicate that the gmhA gene product of H. ducreyi is essential for the expression of wild-type LOS by this pathogen.     

The transcriptional activator HlyU of Vibrio cholerae: nucleotide sequence and role in virulence gene expression

HlyU upregulates expression of the haemolysin, HlyA, of Vibrio cholerae. DNA sequence analysis indicates that HlyU is an 11.9 kDa protein containing a putative helix-turn-helix motif and belonging to a family of small regulatory proteins, including NoIR (Rhizobium meliloti), SmtB (Synechococcus PCC 7942) and ArsR (plasmids R773, Escherichia coli; pI258, Staphylococcus aureus; and pSX267, Staphylococcus xylosus). An hlyU mutant was constructed by insertional inactivation, and found to be deficient in the production of both the haemolysin and a 28 kDa secreted protein. The mutant was assessed for virulence in the infant mouse cholera model, revealing a 100-fold increase in the LD50. This suggests that HlyU promotes expression of virulence determinant(s) in vivo.     

Impact of either elevated or decreased levels of cytochrome bd expression on Shigella flexneri virulence

Shigella spp. are the major cause of bacillary dysentery worldwide. The pathogenic process involves bacterial invasion and lysis of the phagocytic vacuole, followed by replication and movement within the cell cytoplasm and, ultimately, spread directly into adjacent cells. This study demonstrates that S. flexneri cytochrome bd expression is necessary for normal intracellular survival and virulence. Cytochrome bd is one of two terminal oxidases in the bacterial respiratory chain that reduce molecular oxygen to water, utilizing intermediates shuttled through the electron transport chain. S. flexneri mutants that contain a disruption in the cydC locus, which leads to defective cytochrome bd expression, or in the riboflavin (ribE) or ubiquinol-8 (ubiH) biosynthetic pathway, which leads to elevated cytochrome bd expression, were evaluated in intracellular survival and virulence assays. The cydC mutant formed significantly smaller plaques, had significantly decreased intracellular survival, and had a 100-fold increase in lethal dose for mice compared with the wild type. The ribE and ubiH mutants each formed significantly larger plaques and had a 10-fold decrease in lethal dose for mice compared with the wild type. The data indicate that expression of cytochrome bd is required for S. flexneri intracellular survival and virulence.