# Antimycobacterial Mechanisms and Anti-Virulence Activities of Polyphenolic-Rich South African Medicinal Plants Against Mycobacterium smegmatis

## TL;DR

This study explores South African medicinal plants for their potential to combat TB by inhibiting bacterial growth and virulence.

## Contribution

The study identifies polyphenolic-rich plant extracts with strong antimycobacterial and anti-virulence effects against Mycobacterium smegmatis.

## Key findings

- Tarchonanthus camphoratus and Combretum hereroense showed strong antioxidant activity.
- Senecio macroglossus, Nerium oleander, and Tetradenia riparia exhibited potent antimycobacterial activity with MIC = 0.16 mg/mL.
- Most plant extracts significantly impaired bacterial motility and biofilm formation.

## Abstract

The rise of multidrug-resistant tuberculosis (TB) necessitates alternative therapeutic sources. This study investigated the polyphenolic content and the antioxidant, antimycobacterial, and anti-virulence activities of selected medicinal plants traditionally used to treat TB and related symptoms. Total phenolics, tannins, and flavonoids were quantified using colorimetric assays. Antioxidant capacity was assessed via DPPH and ferric-reducing power assays. Antimycobacterial activity against Mycobacterium smegmatis was evaluated using broth microdilution, growth kinetics, cell constituent leakage, and respiratory chain dehydrogenase inhibition assays. Anti-virulence effects were examined using crystal violet biofilm and swarming motility assays. Tarchonanthus camphoratus showed the highest polyphenolic levels and, together with Combretum hereroense, strong antioxidant activity. Extracts of Senecio macroglossus, Nerium oleander, and Tetradenia riparia displayed potent antimycobacterial activity (MIC = 0.16 mg/mL), characterized by delayed exponential growth, membrane damage, and metabolic inhibition. Tabernaemontana elegans exhibited the weakest activity (MIC > 2.5 mg/mL). Most extracts also significantly impaired motility (12–100%) and early-stage biofilm formation. Polyphenolic-rich plant extracts demonstrated promising antimycobacterial and anti-virulence properties against M. smegmatis, highlighting their potential as leads for developing novel anti-TB agents.