Antimicrobial activity of bovine lactoferrin against Gardnerella species clinical isolates

Abstract

Gardnerella species play a key role in the development and recurrence of Bacterial Vaginosis (BV), a common imbalance of the vaginal microbiota. Because of the high rates of BV recurrence reported after treatment with standard of care antibiotics, as well as the emergence of antibiotic-resistant BV, the development of alternative treatment approaches is needed. Bovine lactoferrin, a well studied iron-binding glycoprotein with selective antimicrobial activity, may ameliorate vaginal dysbiosis either alone or in combination with antibiotics. The present study evaluated the antimicrobial resistance/susceptibility profile of seventy-one presumptive G. vaginalis clinical isolates to metronidazole and clindamycin. In addition, the in vitro antimicrobial activity of Metrodora Therapeutics bovine Lactoferrin (MTbLF) against the tested clinical isolates, both alone and in combination with metronidazole and clindamycin, was in depth evaluated using defined-iron culture conditions. All 71 presumptive G. vaginalis clinical isolates exhibited resistance to metronidazole, with MIC values greater than 256 μg/ml. Different susceptibility profiles were detected for clindamycin. In detail, the vast majority of the tested strains (45%), exhibiting MIC lower than 2 μg/ml, were considered sensitive; 18 strains (25%) with MIC higher or equal to 8 μg/ml, were classified as resistant, whereas the remaining 21 (30%) were classified as intermediate. MTbLF was tested in culture medium at different concentrations (32, 16, 8, 4, 2, 1, and 0.5 mg/ml) showing ability to inhibit the growth of the tested presumptive G. vaginalis clinical isolates, including those metronidazole-resistant, in a dose-dependent and not in a strain-dependent manner. MTbLF, at concentrations ranging from 32 to 8 mg/ml, exerted a statistically different antimicrobial activity compared with lower concentrations (4, 2, 1, and 0.5 mg/ml). A synergistic effect between MTbLF (8 and 4 mg/ml) and clindamycin was revealed for all the tested strains. When tested in the absence of other sources of iron, MTbLF did not support the growth of the tested presumptive G. vaginalis clinical isolates. Bovine lactoferrin may be a potential candidate to treat Gardnerella species infection.

Fighting polymicrobial biofilms in bacterial vaginosis

“…Prebiotics have also been tested in combination with antibiotics. Very recently was studied the antimicrobial activity of bovine lactoferrin alone or in combination with metronidazole or clindamycin against G. vaginalis isolates, and the results showed inhibition of Gardnerella growth in a dose‐dependent effect and the combination with clindamycin resulted in a synergistic effect (Pino et al, 2022 ).…”

Proteolysis of vaginally administered bovine lactoferrin: clearance, inter-subject variability, and implications for clinical dosing

“…Proteolysis was stopped at the time points indicated by mixing with SDS PAGE sample buffer and heating to 90 °C iron-binding capacity persists for that duration. Moreover, our recent in vitro experiments (Pino et al 2022) have shown that MTbLF has antimicrobial activity against clinical isolates of Gardnerella vaginalis, a key pathogen in the development and recurrence of BV. The ratio of 80 kDa bLF to its 43 kDa and 37 kDa fragments remains high (> 80%) over at least the first 12 h of the time course while the tablet is in the Dissolution phase or early Washout phase.…”

Oral Intake of the Commercial Probiotic Blend Synbio® for the Management of Vaginal Dysbiosis

“…First-line treatment for BV includes the use of topical or systemic antibiotics, such as metronidazole and clindamycin, whereas polyenes (e.g., nystatin) and azoles are usually administrated in the case of VVC [14]. Unfortunately, antibiotics and antifungal drugs are not always effective, since the microorganisms responsible for BV and VVC can resist these treatments by forming biofilms or by acquiring resistance [15,16]. In addition, antibiotics do not act selectively on the causative agent of the infection and negatively affect endogenous lactobacilli, in turn promoting BV and potentially VVC recurrence [17].…”