No abstract

Bacterial resistances to diverse metals and antibiotics are often genetically linked, suggesting that exposure to toxic metals may select for strains resistant to antibiotics and vice versa. To test the hypothesis that resistances to metals and antibiotics are coselected for in environmental microbial assemblages, we investigated the frequency of diverse resistances in freshwater microcosms amended with Cd, Ni, ampicillin or tetracycline. We found that all four toxicants significantly increased the frequency of bacterioplankton resistance to multiple, chemically unrelated metals and antibiotics. An ampicillin-resistant strain of the opportunistic human pathogen Ralstonia mannitolilytica was enriched in microcosms amended with Cd. Frequencies of antibiotic resistance were elevated in microcosms with metal concentrations representative of industry and mining-impacted environments (0.01-1 mM). Metal but not antibiotic amendments decreased microbial diversity, and a weeklong exposure to high concentrations of ampicillin (0.01-10 mg l-1) and tetracycline (0.03-30 mg l-1) decreased microbial abundance only slightly, implying a large reservoir of antibiotic resistance in the studied environment. Our results provide first experimental evidence that the exposure of freshwater environments to individual metals and antibiotics selects for multiresistant microorganisms, including opportunistic human pathogens.

Defects in DNA mismatch repair (MMR) occur frequently in natural populations of pathogenic and commensal bacteria, resulting in a mutator phenotype. We identified a unique genetic element in Streptococcus pyogenes strain SF370 that controls MMR via a dynamic process of prophage excision and reintegration in response to growth. In S. pyogenes, mutS and mutL are organized on a polycistronic mRNA under control of a common promoter. Prophage SF370.4 is integrated between the two genes, blocking expression of the downstream gene (mutL) and resulting in a mutator phenotype. However, in rapidly growing cells the prophage excises and replicates as an episome, allowing mutL to be expressed. Excision of prophage SF370.4 and expression of MutL mRNA occur simultaneously during early logarithmic growth when cell densities are low; this brief window of MutL gene expression ends as the cell density increases. However, detectable amounts of MutL protein remain in the cell until the onset of stationary phase. Thus, MMR in S. pyogenes SF370 is functional in exponentially growing cells but defective when resources are limiting. The presence of a prophage integrated into the 5 end of mutL correlates with a mutator phenotype (10 ؊7 to 10 ؊8 mutation/generation, an approximately a 100-fold increase in the rate of spontaneous mutation compared with prophage-free strains [10 ؊9 to 10 ؊10 mutation/generation]). Such genetic elements may be common in S. pyogenes since 6 of 13 completed genomes have related prophages, and a survey of 100 strains found that about 20% of them are positive for phages occupying the SF370.4 attP site. The dynamic control of a major DNA repair system by a bacteriophage is a novel method for achieving the mutator phenotype and may allow the organism to respond rapidly to a changing environment while minimizing the risks associated with long-term hypermutability.

This study examined the occurrence of alcohol use to manage pain in community-dwelling adults with tooth pain, jaw joint/face pain, and arthritis. Race/ethnicity, sex, and age were examined to determine their associations with alcohol use for pain. Community-dwelling adults from South Florida with tooth pain (n=1767), jaw joint/face pain (n=1199), or arthritis pain (n=1355) completed a structured telephone interview. Logistic regression models indicted that, similar to population rates, non-Hispanic Whites and males were the most likely to use alcohol to manage pain. In addition, alcohol use for pain was highest in younger adults. Individuals who self-managed oral pain with alcohol were more likely to use prescription and over-the-counter pain medications, but this association was not found for arthritis. Additional characteristics of individuals who self-medicated regardless of pain condition included greater pain frequency, depression, and higher levels of education. Being married was protective against the use of alcohol to manage pain symptoms. Use of alcohol for pain should be assessed during treatment evaluation so that physicians and other health care providers are aware of their patient’s use of alcohol and pain medication concomitantly, assess for psychosocial impairment, and make the appropriate referrals and adjustment to treatment. Perspective Self-medication of pain with alcohol is most common among younger non-Hispanic White males and associated with pain frequency, depression, and use of pain medications. Alcohol use for pain needs to be assessed so that health care providers can make appropriate referrals and adjustments to treatment.