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Competitive fates of bacterial social parasites: persistence and self-induced extinction of Myxococcus xanthus cheaters.

Cooperative biological systems are susceptible to disruption by cheating. Using the social bacterium Myxococcus xanthus, we have tested the short-term competitive fates of mixed cheater and wild-type strains over multiple cycles of cooperative development. Cheater/wild-type mixes underwent several cycles of starvation-induced multicellular development followed by spore germination and vegetative population growth. The population sizes of cheater and wild-type strains in each pairwise mixture were measured at the end of each developmental phase and each growth phase. Cheater genotypes showed several distinct competitive fates, including cheater persistence at high frequencies with little effect on total population dynamics, cheater persistence after major disruption of total population dynamics, self-extinction of cheaters with wild-type survival, and total population extinction. Our results empirically demonstrate that social exploitation can destabilize a cooperative biological system and increase the risk of local extinction events.

Biological Evolution↗

Response to antifungal therapy by human immunodeficiency virus-infected patients with disseminated Penicillium marneffei infections and in vitro susceptibilities of isolates from clinical specimens.

Eighty-six patients with laboratory evidence of human immunodeficiency virus infection presented to Chiang Mai University Hospital in Chiang Mai, Thailand, between 1 June 1990 and 30 June 1992 with systemic infection caused by the dimorphic fungus Penicillium marneffei. Thirty isolates of P. marneffei from clinical specimens from these patients were tested for their in vitro susceptibilities to amphotericin B, 5-fluorocytosine, miconazole, ketoconazole, itraconazole, and fluconazole. P. marneffei was highly susceptible to miconazole, itraconazole, ketoconazole, and 5-fluorocytosine. Amphotericin B showed intermediate antifungal activity, while fluconazole was the least active; some strains of the fungus were resistant to fluconazole. The clinical and microbiological responses correlated with the overall patterns of in vitro susceptibility to the azoles, whereas results with amphotericin B were more difficult to assess. Antibiotic failures of initial therapy occurred in 8 of 35 (22.8%) patients treated with amphotericin B, 3 of 12 (25%) patients treated with itraconazole, and 7 of 11 (63.6%) patients treated with fluconazole. Itraconazole or ketoconazole should be considered to be the drug of first choice in the treatment of mild to moderately severe P. marneffei infection. Parenteral therapy with amphotericin B may be required for seriously ill patients. Since at least 12 patients who responded to initial therapy relapsed within 6 months regardless of initial antifungal therapy, maintenance oral therapy with itraconazole or ketoconazole may be necessary.

Acquired Immunodeficiency Syndrome↗

Evaluation of the efficacy of ciprofloxacin against Streptococcus pneumoniae by using a mouse protection model.

A mouse protection model was used to investigate the association of the pharmacokinetics and pharmacodynamics with the in vivo efficacy of ciprofloxacin compared with that of penicillin G in the treatment of mice infected with Streptococcus pneumoniae ATCC 6303. Mice were inoculated intraperitoneally with 10 times the minimum lethal dose of S. pneumoniae. For determination of the 50% protective dose, subcutaneous antibiotics were begun 1 h after infection and were continued for 24 h. The 50% protective doses of ciprofloxacin and penicillin G were 25.52 +/- 1.95 and 0.307 +/- 0.006 mg/kg of body weight, respectively, an 83-fold difference in efficacy. For 100% protection with penicillin G, the time that the drug concentration needed to remain above the MIC was 51 min, a value easily achieved in most clinical situations. For 100% protection with ciprofloxacin, the peak concentration/MIC ratio must reach a value of 10.6. This ratio is rarely achieved with this drug against S. pneumoniae in clinical practice. These pharmacodynamic differences probably contribute to the reported differences in clinical success between these agents.

Animals↗

Use of in-house studies of molecular epidemiology and full species identification for controlling spread of vancomycin-resistant Enterococcus faecalis isolates.

Infection with multidrug-resistant (MDR) organisms is a major clinical challenge, and few, if any, therapeutic options remain available. Increasingly, infection control measures have taken on greater importance in preventing the nosocomial transmission of MDR organisms. During December 1994 and January 1995, we identified a cluster of vancomycin-resistant Enterococcus faecalis isolates involving 16 patients situated in different areas of our university-affiliated teaching hospital. Initial review of laboratory requisition forms for the patients' locations revealed no common association, suggesting that the occurrence was not due to horizontal spread. However, using genomic DNA extraction, restriction enzyme analysis, and gel electrophoresis, we found that 12 patients were infected with isolates originating from a single clone, 2 other patients were infected with isolates from a different clone, and the remaining 2 patients were infected with unique strains. Because the typing data suggested nosocomial spread, chart review was undertaken to determine a possible common exposure source. With three exceptions, clonal isolates were linked to patient movement between surgical floors, intensive care units, and a rehabilitation unit. A detailed review of patient records revealing the association would not have been performed without realization of clonality. Thus, the data demonstrate the utility of genomic typing for epidemiological purposes. In turn, targeted infection control measures that halted the spread of the potentially lethal MDR pathogen were instituted.

Anti-Bacterial Agents↗

The use of honey as an antiseptic in managing Pseudomonas infection.

A laboratory study was undertaken to extend existing knowledge about the effectiveness of the antibacterial properties of honey against pseudomonads. To date, sensitivity testing has used non-standardised honeys, which may vary greatly in their antibacterial potency. Pure cultures of Pseudomonas spp, isolated from swabs from 20 infected wounds, were inoculated on the surface of nutrient agar plates containing various concentrations of honey in the medium. Two types of honey were used, a manuka honey and a pasture honey, each selected to have antibacterial activity close to the median for each type. The minimum inhibitory concentration of the manuka honey for the 20 isolates ranged from 5.5-8.7% (v/v) (mean 6.9% (v/v), standard deviation 1.3). The minimum inhibitory concentration of the pasture honey for the 20 isolates ranged from 5.8-9.0% (v/v) (mean 7.1% (v/v), standard deviation 1.0). Honeys with an average level of antibacterial activity could be expected to be effective in preventing the growth of pseudomonads on the surface of a wound even if the honey were diluted more than ten-fold by exudation from the wound.

Anti-Infective Agents, Local↗

Health risks associated with wastewater irrigation: an epidemiological study.

An analysis of morbidity was made in 11 kibbutzim (cooperative agricultural settlements), with a total population of 3,040, that had switched from nonwastewater to wastewater sprinkler irrigation or vice versa. Generally, partially treated stabilization pond effluent of poor microbial quality was used for irrigation. Vegetables or salad crops were not irrigated with effluent. The results showed that a seasonal, twofold, excess risk of "enteric" disease was found in the 0 to 4 year-old age group during the summer irrigation months in those years in which wastewater was used for irrigation, compared with the parallel summer months of nonwastewater irrigation years in the same kibbutz. On the year round rates basis, little or no excess enteric disease was found in wastewater irrigating communities.

Adolescent↗

Emerging infectious diseases at the beginning of the 21st century.

The emergence and re-emergence of infectious diseases involves many interrelated factors. Global interconnectedness continues to increase with international travel and trade; economic, political, and cultural interactions; and human-to-human and animal-to-human interactions. These interactions include the accidental and deliberate sharing of microbial agents and antimicrobial resistance and allow the emergence of new and unrecognized microbial disease agents. As the 21st century begins, already new agents have been identified, and new outbreaks have occurred. Solutions to limiting the spread of emerging infectious diseases will require cooperative efforts among many disciplines and entities worldwide. This article defines emerging infectious diseases, summarizes historical background, and discusses factors that contribute to emergence. Seven agents that have made a significant appearance, particularly in the 21st century, are reviewed, including: Ebola and Marburg hemorrhagic fevers, human monkeypox, bovine spongiform encephalopathy, severe acute respiratory syndrome (SARS), West Nile virus, and avian influenza. The article provides for each agent a brief historical background, case descriptions, and health care implications.

Animals↗

Penicillin-induced killing and postantibiotic effect in oral streptococci are enhanced by platelet microbicidal proteins.

Thrombin-induced platelet microbicidal proteins (tPMP) are alpha-granule-derived cationic antimicrobial proteins released from platelets by stimulation with thrombin. tPMP has potent microbicidal activities against a broad spectrum of common microbial pathogens in infective endocarditis. We studied in vitro interactions of tPMP with penicillin against oral streptococci, Streptococcus rattus BHT (a tPMP-susceptible organism) and Streptococcus gordonii DL1 (a tPMP-insusceptible organism). tPMP was prepared by stimulating rabbit platelets with thrombin. tPMP plus penicillin showed a synergistic bactericidal effect on both S. rattus BHT and S. gordonii DL1, in contrast to either agent alone. Sequential exposure of both S. rattus BHT and S. gordonii DL1 to tPMP followed by exposure to penicillin at 10x the MICs resulted in a significant extension of the postantibiotic-effect duration compared with antibiotic exposure alone. The combined data indicate that tPMP exerts cooperative bactericidal and growth-inhibiting effect in concert with penicillin.

Animals↗

An outbreak of infection caused by trimethoprim-resistant coliform bacilli in a geriatric unit.

An outbreak of infections, particularly of the urinary tract, caused by coliform bacilli resistant to trimethoprim, and originating in a geriatric unit, is described. The investigation of the outbreak and the analysis of factors predisposing to asymptomatic carriage of trimethoprim-resistant coliform bacilli enabled successful control measures to be initiated. The significance of geriatric units as sources of hospital infection is discussed. The importance of cooperation between geriatricians, infection control nurses and microbiologists is emphasized.

Aged↗

Natural killer cells: emerging concepts in immunity to infection and implications for assessment of immunodeficiency.

PURPOSE OF REVIEW: As the molecular networks that connect innate and adaptive immunity are untangled, the prominence of natural killer (NK) cells in host defense continues to emerge. Herein we highlight recent findings pertaining to NK cell development, trafficking, and interactions with other innate and adaptive immune cells in the context of predicting how NK cells may be involved in a wider range of clinical immunodeficiency. RECENT FINDINGS: NK cells contribute vital roles in innate and adaptive immunity, especially in collaboration with dendritic cells (DC). Fascinating new details have been reported about cell surface integrins and receptors that regulate NK functions, as well as the cytokine/chemokine networks that provide for NK-DC interactions. Moreover, NK cells appear to play an important role in the attenuation or resolution of an immune response through either action against CD8 T cells or indirect control of certain DC. These findings shed important insights as to how NK cells and DC cooperate to control primary infections and shape the subsequent adaptive immune responses. SUMMARY: Natural killer cells are heterogeneous lymphocytes that provide an essential function in host defense. NK cells respond early to microbial assault and interact with other cells of the innate immune system, but they recognize and intercept pathogenic infections through highly specific mechanisms that are similar to T cells. Thus, NK cells are positioned as a cellular bridge between innate and adaptive immunity. It is imperative, then, to include a careful assessment of NK cell populations and functions in most cases of suspected immunodeficiency.

Animals↗

In vitro fermentation of sugar beet arabinan and arabino-oligosaccharides by the human gut microflora.

AIMS: To determine the fermentation profiles by human gut bacteria of arabino-oligosaccharides of varying degree of polymerization. MATERIALS AND METHODS: Sugar beet arabinan was hydrolyzed with a commercial pectinase and eight fractions, of varying molecular weight, were isolated by gel-filtration chromatography. Hydrolysis fractions, arabinose, arabinan and fructo-oligosaccharides were fermented anaerobically by gut bacteria. Total bacteria, bifidobacteria, bacteroides, lactobacilli and the Clostridium perfringens/histolyticum sub. grp. were enumerated using fluorescent in situ hybridization. RESULTS: Bifidobacteria were stimulated to different extents depending on molecular weight, i.e. maximum increase in bifidobacteria after 48 h was seen on the lower molecular weight fractions. Lactobacilli fluctuated depending on the initial inoculum levels. Bacteroides numbers varied according to fraction; arabinan, arabinose and higher oligosaccharides (degree of polymerization, dp > 8) resulted in significant increases at 24 h. Only carbohydrate mixtures with dp of 1-2 resulted in significant increases at 48 h (log 8.77 +/- 0.23). Clostridia decreased on all substrates. CONCLUSIONS: Arabino-oligosaccharides can be considered as potential prebiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: Arabinan is widely available as it is a component of sugar beet pulp, a co-product from the sugar beet industry. Generation of prebiotic functionality from arabinan would represent significant added value to a renewable resource.

Arabinose↗

The erythromycin resistance gene from the Bacteroides conjugal transposon Tcr Emr 7853 is nearly identical to ermG from Bacillus sphaericus.

Tcr Emr 7853, from Bacteroides thetaiotaomicron 7853, is a large chromosomal conjugative transposon which encodes resistance to both tetracycline (Tcr) and erythromycin (Emr). The erythromycin resistance gene of Tcr Emr 7853 did not cross-hybridize with ermF, the Emr gene found on previously studied Bacteroides regular and conjugative transposons. We have cloned and sequenced the erythromycin resistance gene from Tcr Emr 7853. The DNA sequence of this gene was 99.6% identical to that of ermG from Bacillus sphaericus.

Bacillus↗

Protective effect of recombinant human interleukin-2 against lethal infection caused by Klebsiella pneumoniae.

The effects of recombinant human interleukin-2 (rIL-2) administered prophylactically on the death of CBA/J mice challenged with Klebsiella pneumoniae 27 intraperitoneally were examined. rIL-2 administered subcutaneously at 20 micrograms per mouse for 7 days enhanced survival after a lethal challenge. The injection of anti-asialo GM1 antibody did not influence the effect of rIL-2. In mice given rIL-2, the number of peritoneal macrophages increased, and the infiltration of polymorphonuclear leukocytes (PMN) into the peritoneal cavity after the bacterial challenge was enhanced. In addition, adoptive transfer of sera and peritoneal exudate cells (PEC), consisting of an approximately equal number of macrophages and PMN, obtained from mice given rIL-2 enhanced resistance to a K. pneumoniae infection, compared with adoptive transfer of sera and PEC obtained from mice not given rIL-2. These results indicate that rIL-2 protects mice from a lethal challenge with K. pneumoniae, and suggest that the protective effect is due to an increase in the number of phagocytic cells and in the cooperative activity of the sera and the phagocytic cells.

Animals↗