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31.
Gareth McVicker Tomasz K. Prajsnar Alexander Williams Nelly L. Wagner Michael Boots Stephen A. Renshaw Simon J. Foster 《PLoS pathogens》2014,10(2)
To slow the inexorable rise of antibiotic resistance we must understand how drugs impact on pathogenesis and influence the selection of resistant clones. Staphylococcus aureus is an important human pathogen with populations of antibiotic-resistant bacteria in hospitals and the community. Host phagocytes play a crucial role in controlling S. aureus infection, which can lead to a population “bottleneck” whereby clonal expansion of a small fraction of the initial inoculum founds a systemic infection. Such population dynamics may have important consequences on the effect of antibiotic intervention. Low doses of antibiotics have been shown to affect in vitro growth and the generation of resistant mutants over the long term, however whether this has any in vivo relevance is unknown. In this work, the population dynamics of S. aureus pathogenesis were studied in vivo using antibiotic-resistant strains constructed in an isogenic background, coupled with systemic models of infection in both the mouse and zebrafish embryo. Murine experiments revealed unexpected and complex bacterial population kinetics arising from clonal expansion during infection in particular organs. We subsequently elucidated the effect of antibiotic intervention within the host using mixed inocula of resistant and sensitive bacteria. Sub-curative tetracycline doses support the preferential expansion of resistant microorganisms, importantly unrelated to effects on growth rate or de novo resistance acquisition. This novel phenomenon is generic, occurring with methicillin-resistant S. aureus (MRSA) in the presence of β-lactams and with the unrelated human pathogen Pseudomonas aeruginosa. The selection of resistant clones at low antibiotic levels can result in a rapid increase in their prevalence under conditions that would previously not be thought to favor them. Our results have key implications for the design of effective treatment regimes to limit the spread of antimicrobial resistance, where inappropriate usage leading to resistance may reduce the efficacy of life-saving drugs. 相似文献
32.
Mitochondrial DNA (mtDNA) sequences that include (a) a part of the
cytochrome b gene, (b) two tRNA genes, and (c) a part of the noncoding
D-loop region of 31 Anguilla japonica (Japanese eel) and 1 A. marmorata
collected from Taiwan, Japan, and mainland China were determined to
evaluate the population structure of Japanese eel. Among 30 genotypes
identified from the 31 Japanese eel mtDNAs sequenced, there are 58 variable
sites, predominantly clustered at the D-loop region. The phylogenetic tree
constructed by the unweighted pair-group method with arithmetic mean shows
neither significant genealogical branches nor geographic clusters.
Furthermore, the sequence-statistics test reveals little, if any,
significant genetic differentiation. These results indicate that the 31
Japanese eels might come from a single population. Analysis of sequence
variation in mtDNA by using the relationship between the number of
segregating sites and the average number of nucleotide differences under
the neutral mutation hypothesis reveals that neutral mutation acts as a
major factor influencing the evolutionary divergence of the Japanese eel
mitochondrial genome sequenced, especially in the noncoding region.
相似文献
33.
Wei S Lian Heng Lin Winston TK Cheng Tateki Kikuchi Ching F Cheng 《Journal of biomedical science》2011,18(1):26