Researchers Identify How Vaginal Microbiome Can Elicit Resistance or Susceptibility to Chlamydia

Institute for Genome Sciences Scientists at UM School of Medicine Shed Light on How Certain Vaginal Microbiome Can Help Protect Against Sexually Transmitted Infections

The vaginal microbiome is believed to protect women against Chlamydia trachomatis, the etiological agent of the most prevalent sexually transmitted infections (STIs) in developed countries. New research by the University of Maryland School of Medicine (UMSOM) shows how the microbiome can either protect or make a woman more susceptible to these serious infections.

The research is important amid a rising number of cases of chlamydia worldwide. In the U.S. alone, 1.7 million cases of chlamydia were reported in 2017, a 22% increase since 2013, according to data from the Centers for Diseases Control and Prevention (CDC).

“Chlamydia is a major growing health issue in the U.S., and more work is needed to understand why some women are apparently naturally protected while other are not,” commented Jacques Ravel, PhD, Professor of Microbiology and Immunology, Associate Director and Senior Scientist at the Institute for Genome Sciences (IGS) at UMSOM. Dr. Ravel is also a Principal Investigator for this research. “Our novel research aims to decipher the mechanistic and functional underpinnings of communication between the host and the cervicovaginal microbiome to better understand resistance and susceptibility to this infection.”

An Important Mechanism in Vaginal Microbiome

While Lactobacillus-dominated microbiota in a woman’s vagina has long been suspected to provide a protective barrier against STIs like chlamydia, investigators at IGS and the University of Maryland School of Dentistry (UMSOD) are reporting for the first time a mechanism enabling specific types of cervicovaginal microbiome to predispose cells in the vagina and cervix to resist chlamydial infection.

“We will now be able to leverage these microbiomes to identify women at risk of infections, but more importantly to develop improved strategies to restore an optimal protection when it is lacking. Unlike our genes, the vaginal microbiome can be modulated to increase protection against chlamydia, but also against other sexually transmitted infections, including HIV,” said Dr. Ravel of the research, which was published today in mBio, “Cervicovaginal Microbiota-Host Interaction Modulates Chlamydia trachomatis Infection.”

The investigators have shown previously that five major types of vaginal microbiome exist, four of which are dominated by a different species of Lactobacillus, while the fifth has very low numbers of Lactobacillus bacteria and is associated with an increased risk of adverse outcomes including STIs, such as HIV, and even premature births.

The current research showed that Lactobacillus iners, a bacterium actually commonly found in the vagina did not optimally protect human cells against chlamydial infection, while products of Lactobacillus crispatus, another Lactobacillus species frequently found in the vagina, did.

Previously published research has hinted at L. iners being a risk factor for STI; however, the mechanism by which these bacteria were specifically suboptimal at protecting women against STI has remained elusive. Like other Lactobacillus, L. iners produces lactic acid, but only the L isoform. The researchers found that D-lactic acid, not L-lactic acid, down-regulates cell cycling through epigenetic modifications thus blocking C. trachomatis entry into the cell, one of the pathogen key infectious process, among other processes.

Thus, a rather unexpected result of this study is that the vaginal microbiome does not affect the pathogen per se, but drives susceptibility or resistance to infection, by modifying the cells that line up the cervicovaginal epithelium. The researchers further demonstrated that exposure to optimal vaginal microbiota provided long term protection, which has major implication on how a woman is protected. These mechanisms are now being exploited to develop strategies to optimize protection against C. trachomatis infections but also other STIs.

Patrik Bavoil, PhD, Professor & Chair, Department of Microbial Pathogenesis, University of Maryland School of Dentistry, a well-known expert in C. trachomatis biology and pathogenesis, is a Co-Principal Investigator with Dr. Ravel on the NIH funding that supported this study. The investigators also collaborated with Larry Forney, PhD at the University of Idaho.

“Chlamydia is reputed to be a most difficult microorganism to study. By hiding inside cells, the pathogen routinely avoids antimicrobial host defenses. By causing mostly asymptomatic infection, it often escapes detection by both the infected host and the physician alike,” said Dr. Bavoil. “What we have done in this study through several years of hard work by dedicated researchers is to provide, for the first time, a huge, new stepping stone on which future translational research to exploit the microbiome in the fight against chlamydial infection and disease, can be based.”

This research was supported by the National Institute for Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under award numbers U19A1084044 and UH2A1083264.

“This groundbreaking research will stimulate the development of novel antibiotic sparing solution to modulate the cervicovaginal microbiota to protect women from STI, but also from adverse reproductive outcomes such as preterm birth,” said UMSOM Dean E. Albert Reece, MD, PhD, MBA, who is also the Executive Vice President for Medical Affairs, University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor.

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world, with 43 academic departments, centers, institutes, and programs. The School of Medicine has a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished recipient of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.2 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for more than 1.2 million patients each year. The School has over 2,500 students, residents, and fellows, and nearly $575 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total workforce of nearly 7,000 individuals. The combined School and Medical System (“University of Maryland Medicine”) has an annual budget of over $6 billion and an economic impact of more than $15 billion on the state and local community. The School of Medicine faculty, which ranks as the 8th highest among public medical schools in research productivity, is an innovator in translational medicine, with 600 active patents and 24 start-up companies. The School works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu

About the Institute for Genome Sciences

The Institute for Genome Sciences, founded in 2007, is an international research center within the University of Maryland School of Medicine. Comprised of an interdisciplinary, multidepartment team of investigators, the Institute uses the powerful tools of genomics and bioinformatics to understand genome function in health and disease, to study molecular and cellular networks in a variety of model systems, and to generate data and bioinformatics resources of value to the international scientific community.
igs.umaryland.edu

About the University of Maryland School of Dentistry

The University of Maryland School of Dentistry, the world’s first dental college, offers superlative educational programs in oral health. As one of six professional schools and an interdisciplinary Graduate School on the University of Maryland, Baltimore’s 71-acre campus, it is part of a thriving academic health center that combines groundbreaking biomedical research and exceptional patient care. The school is Maryland’s predominant provider of comprehensive and emergency oral health services. dental.umaryland.edu