October 8, 2015
Specific microbes appear to strengthen a woman’s natural physical barriers against sexually transmitted infections like HIV, according to researchers at the UNC Eshelman School of Pharmacy at the University of North Carolina at Chapel Hill.
The mucus lining of the cervix and vagina is a woman’s first line of defense against sexually transmitted infections. A research team led by Sam Lai, Ph.D., senior author of the study and an assistant professor at the pharmacy school, has shown that the amount of protection offered may depend on the type of helpful bacteria present in the mucus.
“We set out to understand why the barrier properties of cervicovaginal mucus vary among women or even in the same woman,” Lai said. “We found that vaginal microorganisms, including specific species of lactobacillus bacteria, can directly alter the protective properties of cervicovaginal mucus.”
The team’s findings were published in mBio, the online open-access journal of the American Society for Microbiology.
Historically the vaginal microbiota has been considered healthy if it was dominated by any species of lactobacillus, Lai said. His team found that a specific species — lactobacillus crispatus — appears to play a key role in sustaining the mucus barrier against HIV and other sexually transmitted infections. These findings could lead to the development of new strategies to protect women against HIV, he said.
The research team examined mucus from 31 women of reproductive age using high-resolution, time-lapse microscopy to test whether fluorescent HIV pseudovirus particles became trapped in the mucus or spread freely. Mucus — the slimy and sticky secretions that line mucosal surfaces — is the body’s first line of defense against pathogens such as viruses.
The researchers observed two distinct types of mucus samples: one that was very good at trapping HIV and one that did not. Trapping of HIV did not correlate to the mucus’ pH, total lactic acid, or Nugent score, which is a rough measure of vaginal health that reflects how much lactobacillus bacteria is present compared to other microbes.
However, one difference between the two groups did stand out: higher levels of D-lactic acid in the group that trapped HIV. Humans cannot make D-lactic acid, so the team suspected that bacteria living within the mucus layer were responsible for the difference. The researchers found that mucus that trapped HIV had predominantly lactobacillus crispatus. Samples that did not trap HIV were either dominated by lactobacillus iners or had multiple bacterial species present including gardnerella vaginalis, both conditions that are frequently associated with bacterial vaginosis. The majority of women in developing countries, including those in Africa, have vaginal microbiota that are either dominated by lactobacillus iners or microbes associated with bacterial vaginosis, Lai said.
To reinforce the mucus barrier against pathogens, Lai is also working to immobilize pathogens in mucus using antibodies either delivered directly to mucosal surfaces or elicited by vaccines. In 2014 his lab discovered that IgG antibodies can be harnessed to trap viruses in mucus with exceptional potency and that trapping viruses in mucus alone blocked vaginal herpes transmission in mouse models. His work showing how antibodies can work in tandem with mucus to block infections resulted in him receiving a Packard Fellowship in Science and Engineering and a Career Award from the National Science Foundation.
This work was supported by the National Institutes of Health grants R21AI093242, U19AI096398 U19AI084044, a UNC Center for AIDS Research developmental award (P30 AI50410) and a Diversity Supplement 1F32AI102535, The David and Lucile Packard Foundation and startup funds from the UNC Eshelman School of Pharmacy and UNC Lineberger Comprehensive Cancer Center.
- Kenetta Nunn, M.S., graduate student, UNC/NCSU Joint Department of Biomedical Engineering
- Ying-Ying Wang, Ph.D, postdoctoral fellow in the Department of Biophysics, Johns Hopkins University
- Dimple Harit, research associate, Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy
- Michael Humphrys, lab research specialist, Institute for Genome Sciences, University of Maryland School of Medicine
- Bing Ma, Ph.D., research associate at the Institute for Genome Sciences and Department of Microbiology and Immunology at the University of Maryland School of Medicine
- Richard Cone, Ph.D., professor of biophysics, Johns Hopkins University
- Jacques Ravel, Ph.D., associate director of the Institute for Genome Sciences and professor of microbiology and immunology at the University of Maryland School of Medicine
- Samuel Lai, Ph.D., assistant professor in the Division of Molecular Pharmaceutic, UNC Eshelman School of Pharmacy