Presentation Title

Metabolic response of Lactobacillus iners and Gardnerella vaginalis pure cultures to TDF, an HIV drug

Faculty Mentor

Manjula Gunawardana M.P.H

Start Date

17-11-2018 8:30 AM

End Date

17-11-2018 10:30 AM

Location

CREVELING 31

Session

POSTER 1

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

HIV is a retrovirus that is spread via certain bodily fluids, with 80% infections resulting from sexual contact. This virus targets immune cells, negatively impacting the immune system. One approach to treat HIV infection is with the antiretroviral therapy drug, Tenofovir disoproxil fumarate (TDF). Women are infected disproportionately compared to men, with topical application efficiency of TDF varying between 0% and 39%. A potential cause of the varying result of efficiency would be HIV modifies the vaginal microbiome. Certain bacterial species may have the capability to metabolize TDF, hence reducing efficacy. This investigation focused on how Gardnerella vaginalis and Lactobacillus iners interacted with TDF in its environment and found that they both can uptake TDF and metabolize the compound. HPLC analysis of TDF uptake indicated that, L. iners and G. vaginalis metabolized TDF at varying rates. Given our findings, it is important to further investigate potential low efficacy of anti-HIV therapeutics due to metabolism by vaginal microbiome.

Summary of research results to be presented

From the FISH images, bacteria were present throughout the duration of the experiment. Base on the morphology, the bacteria present in the samples were the target bacteria. From the chromatograms, a pattern is notable for both L. iners and G. vaginalis; the peak area of TDF decreased as the area of the TDF degradation product significantly increased. The identity of the TDF deg had yet to be determined.

The TDF deg concentration increased over time in both bacterial lysates while TDF concentrations decreased. There is a decrease in TDF deg after the 24 hour period for G. vaginalis lysate. This could be caused by low TDF concentration; at the 48 hour period exposure of G. vaginalis to TDF, the concentration of TDF is seen to be very low. G. Vaginalis displays a different TDF uptake pattern from L. iners, which implied the two bacteria may possess different mechanisms for uptaking TDF. The cell-free culture media from L. iners and from G. vaginalis also displayed a similar trend to the lysates; there was a decrease in TDF concentration while there was an increase in TDF deg concentration.

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Nov 17th, 8:30 AM Nov 17th, 10:30 AM

Metabolic response of Lactobacillus iners and Gardnerella vaginalis pure cultures to TDF, an HIV drug

CREVELING 31

HIV is a retrovirus that is spread via certain bodily fluids, with 80% infections resulting from sexual contact. This virus targets immune cells, negatively impacting the immune system. One approach to treat HIV infection is with the antiretroviral therapy drug, Tenofovir disoproxil fumarate (TDF). Women are infected disproportionately compared to men, with topical application efficiency of TDF varying between 0% and 39%. A potential cause of the varying result of efficiency would be HIV modifies the vaginal microbiome. Certain bacterial species may have the capability to metabolize TDF, hence reducing efficacy. This investigation focused on how Gardnerella vaginalis and Lactobacillus iners interacted with TDF in its environment and found that they both can uptake TDF and metabolize the compound. HPLC analysis of TDF uptake indicated that, L. iners and G. vaginalis metabolized TDF at varying rates. Given our findings, it is important to further investigate potential low efficacy of anti-HIV therapeutics due to metabolism by vaginal microbiome.