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. 2020 Sep 30;9(10):661.
doi: 10.3390/antibiotics9100661.

Caerin 1 Antimicrobial Peptides That Inhibit HIV and Neisseria May Spare Protective Lactobacilli

Louise A Rollins-Smith  1 , Patricia B Smith  1 , Anna M Ledeczi  1 , Julia M Rowe  1 , Laura K Reinert  1
Affiliations

Caerin 1 Antimicrobial Peptides That Inhibit HIV and Neisseria May Spare Protective Lactobacilli

Louise A Rollins-Smith et al. Antibiotics (Basel). .

Abstract

Although acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) is a manageable disease for many, it is still a source of significant morbidity and economic hardship for many others. The predominant mode of transmission of HIV/AIDS is sexual intercourse, and measures to reduce transmission are needed. Previously, we showed that caerin 1 antimicrobial peptides (AMPs) originally derived from Australian amphibians inhibited in vitro transmission of HIV at relatively low concentrations and had low toxicity for T cells and an endocervical cell line. The use of AMPs as part of microbicidal formulations would expose the vaginal microbiome to these agents and cause potential harm to protective lactobacilli. Here, we tested the effects of caerin 1 peptides and their analogs on the viability of two species of common vaginal lactobacilli (Lactobacillus rhamnosus and Lactobacillus crispatus). Several candidate peptides had limited toxicity for the lactobacilli at a range of concentrations that would inhibit HIV. Three AMPs were also tested for their ability to inhibit growth of Neisseria lactamica, a close relative of the sexually transmissible Neisseria gonorrhoeae. Neisseria lactamica was significantly more sensitive to the AMPs than the lactobacilli. Thus, several candidate AMPs have the capacity to inhibit HIV and possible N. gonorrhoeae transmission at concentrations that are significantly less harmful to the resident lactobacilli.

Keywords: Amphibian antimicrobial peptide; Lactobacillus crispatus; Lactobacillus rhamnosus; Neisseria lactamica; caerin peptide; human immunodeficiency virus (HIV).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effects of caerin 1 peptides on growth of Lactobacillus rhamnosus. (a,b) Caerin 1.2; (c,d) Caerin 1.9; (e,f) Caerin 1.10; (g,h) Caerin 1.20. Panels on the left show growth as changes in optical density (O.D.) at 630 nm for one representative experiment testing the peptides at increasing 2-fold concentrations from 0.4 or 0.8 to 50 µM. Panels on the right show the average as percent growth in comparison with the positive (no peptide) control set at 100% for replicate experiments for the range of concentrations from 6.25–50 µM. The number of replicate experiments for each peptide is shown in brackets within the panel. * Significantly reduced growth in comparison with the positive control, p < 0.01 by one-way ANOVA with Tukey’s post hoc test.
Figure 2
Figure 2
Effects of caerin 1 peptides on growth of Lactobacillus rhamnosus. (a,b) Caerin 1.1 mod 7; (c,d) Caerin 1.9 sm; (e,f) Caerin 1.3; (g,h) Caerin 1.4. Panels on the left show growth as changes in optical density (O.D.) at 630 nm for one representative experiment testing the peptides at increasing 2-fold concentrations from 0.4 or 0.8 to 50 µM. Panels on the right show the average as percent growth in comparison with the positive (no peptide) control set at 100% for replicate experiments for the range of concentrations from 6.25–50 µM. The number of replicate experiments for each peptide is shown in brackets within the panel. * Significantly reduced growth in comparison with the positive control, p < 0.01 by one-way ANOVA with Tukey’s post hoc test.
Figure 3
Figure 3
Effects of caerin 1 peptides on growth of Lactobacillus crispatus. (a,b) caerin 1.2; (c,d) caerin 1.9; (e,f) caerin 1.10. Panels on the left show growth as changes in optical density (O.D.) at 630 nm for one representative experiment testing the peptides at increasing 2-fold concentrations from 0.4 or 0.8 to 50 µM. Panels on the right show the average as percent growth in comparison with the positive (no peptide) control set at 100% for replicate experiments for the range of concentrations from 6.25–50 µM. The number of replicate experiments for each peptide is shown in brackets within the panel. * Significantly different growth in comparison with the positive control, p < 0.01 by one-way ANOVA with Tukey’s post hoc test.
Figure 4
Figure 4
Effects of caerin 1 peptides on growth of Lactobacillus crispatus. (a,b) caerin 1.3; (c,d) caerin 1.4. Panels on the left show growth as changes in optical density (O.D.) at 630 nm for one representative experiment testing the peptides at increasing 2-fold concentrations from 0.4 or 0.8 to 50 µM. Panels on the right show the average as percent growth in comparison with the positive (no peptide) control set at 100% for replicate experiments for the range of concentrations from 6.25–50 µM. The number of replicate experiments for each peptide is shown in brackets within the panel.
Figure 5
Figure 5
Comparison of the effects of caerin 1 peptides on percent of HIV infection of target T cells (blue) with percent growth of Lactobacillus rhamnosus (red) and Lactobacillus crispatus (green). (a) caerin 1.2; (b) caerin 1.9; (c) caerin 1.10; (d) caerin 1.20. HIV percent infection was previously published (11) and average percent growth of the lactobacilli in the presence of each peptide is new for this study and presented above in Figure 1, Figure 2 and Figure 3.
Figure 6
Figure 6
Comparison of the effects of caerin 1 peptides on percent of HIV infection of target T cells (blue) with percent growth of Lactobacillus rhamnosus (red) and Lactobacillus crispatus (green). (a) caerin 1.3; (b) caerin 1.4; (c) caerin 1.1 mod 7; (d) caerin 1.9 sm. HIV percent infection was previously published [11] and average percent growth of the lactobacilli in the presence of each peptide is new for this study and presented above in Figure 1, Figure 2, Figure 3 and Figure 4.
Figure 7
Figure 7
Effects of caerin 1 peptides on growth of Neisseria lactamica. (a,b) caerin 1.2; (c,d) caerin 1.9; (e,f) caerin 1.10. Panels on the left show growth as changes in optical density (O.D.) at 630 nm for one representative experiment testing the peptides at increasing 2-fold concentrations from 0.8 to 50 µM. Panels on the right show the average as percent growth in comparison with the positive (no peptide) control set at 100% for replicate experiments for the range of concentrations from 6.25–50 µM. The number of replicate experiments for each peptide is shown in brackets within the panel. * Significantly different growth in comparison with the positive control, p < 0.01 by one-way ANOVA with Tukey’s post hoc test.
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