Unknown Bacteria Found in Women With Vaginosis
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Women with bacterial vaginosis appear to play host to about twice as many species of bacteria as previously suspected, reported researchers here.
In addition, 19 of 35 species of bacteria detected in the vaginal fluid of women with bacterial vaginosis appear to be newly identified, reported David N. Fredericks, M.D., and colleagues of the Fred Hutchinson Cancer Research Center and University of Washington, both in Seattle.
Several of these newly identified organisms are common in the vaginal fluid of women with bacterial vaginosis but rare in the fluid obtained from healthy controls, the Seattle team reported in the Nov. 3 issue of the New England Journal of Medicine.
But whether the new-found microorganisms will turn out to be the long-sought perpetrators of bacterial vaginosis or merely innocent bystanders is unclear, commented Sharon L. Hillier, Ph.D., of the University of Pittsburgh in an accompanying editorial.
Many women with vaginosis are asymptomatic, and for others the only symptom may be a malodorous vaginal discharge. The condition, which occurs 10% to 20% of Caucasian women and 30% to 50% of African-American women in the U.S., is often harmless and responds to empiric antibiotic therapy.
Nonetheless, infections are frequently recurrent, and bacterial vaginosis has been associated with premature delivery resulting in low birth weight, pelvic inflammatory disease, and increased risk of HIV transmission.
The problem, vaginosis researchers say, is that they have yet to find the smoking gun that can lead them to the culprit behind the infections.
“With most bacterial infections, you identify what the bacterium is and you treat that bacterium,” said Dr. Fredricks. “The problem with bacterial vaginosis is we don’t know what we’re treating. We know some of the strains associated with bacterial vaginosis, however many strains that are cultured in the lab are not sensitive to the usual antibiotic treatments, yet patients may respond to therapy. We need to find out which bacteria cause bacterial vaginosis and why some women either respond to antibiotic treatment or fail to be cured.”
To see whether they could narrow the field of suspects, the investigators obtained vaginal fluid samples from 27 women with bacterial vaginosis and 46 women without it.
The authors bypassed standard bacterial culture techniques and instead extracted from the samples bacterial DNA, cloned the DNA segments, expanded them with polymerase chain reaction (PCR) and then looked for the 16S ribosomal RNA genes unique to each bacterial species.
The investigators also used fluorescence in situ hybridization (FISH) to confirm that newly recognized bacteria detected by PCR corresponded to the specific bacterial shapes found in the fluid.
They then compared their findings to the NIH’s GenBank database to see whether the strains they detected were known to science.
They found that women without bacterial vaginosis had one to six different vaginal bacterial species, with benign lactobacillus species being most commonly found (83% to 100% of clones).
In contrast, women with bacterial vaginosis had significantly greater bacterial diversity (P<0.001), with nine to 17 different types detected in each sample, with newly recognized species present in 32% to 89% of clones per sample library (mean, 58%).
In all, they found 35 unique bacterial species in the fluid of women with bacterial vaginosis, including several species with no close cultivated relatives, and several of these new species were highly prevalent in women with vaginosis, but not in controls.
“Bacterial vaginosis in our subjects was associated with complex vaginal bacterial communities that included many newly recognized bacterial species that have not previously been detected with conventional cultivation techniques,” Fredericks et al wrote. “We identified three bacterial species in the Clostridiales order that were highly specific for the presence of bacterial vaginosis and only distantly related to known bacteria.”
“The study by Fredricks et al provides important new insights regarding the great variety of dominant microbes present in the ecosystems of women with bacterial vaginosis, but we do not know whether these microorganisms represent innocent colonizers or possible pathogens,” Dr. Hillier wrote in her editorial.
Dr. Hillier pointed out another limitation to the study which was also recognized by the authors.
“Microorganisms present at concentrations of 106 or fewer colony-forming units per gram of vaginal fluid are unlikely to be detected by the PCR approach,” she said. “Thus, the present study provides a better understanding of the numerically dominant microbial populations than is achievable with the use of culture-based methods. Bacteria of known pathogenic potential that are present at concentrations of 103 to 106 colony-forming units per gram of vaginal fluid would not be detected (e.g., group B streptococcus, which is known to be present in the vagina of one in three women, although at a low density, as compared with other microbes). In the context of bacterial vaginosis, high microbial density may not denote pathogenicity.”
Source: New England Journal of Medicine
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