Phytochemicals for bacterial resistance – strengths, weaknesses and opportunities

There are enormous challenges facing the pharmaceutical industry with regard to the burgeoning threat of bacterial multi-drug resistance (MDR). The proliferation of strains of methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, intrinsically resistant Gram-negative bacteria such as Acinetobacter baumannii and extremely-drug resistant Mycobacterium tuberculosis (XDR-TB) [1] are cause for considerable concern. Very few new antibacterials are appearing largely because the markets are both specialist and small, or are for areas of the developing world where the population is unable to pay for expensive new antibiotics. Recent new cases of XDR-TB in the US and Europe and reports of a global increase in patients with strains of MDR-TB will focus attention on the need for new agents to deal with these threats.

Plants are a practically untapped source of potential new antibacterials and some of the literature examples have outstanding preliminary activity [2]. There is also an ecological rationale that plants produce antimicrobial natural products as part of their defence strategy against pathogenic microbes in their environment. Clinical strains of resistant bacteria are also unlikely to have encountered some of the new structural motifs of plant antibacterial, and this would be advantageous [3]. Additionally, some plant antibacterials such as totarol (1) are active against multidrug-resistant strains and are also inhibitors of the multidrug-resistance that characterises these strains. This dual mode of action would suggest that there is considerable prospect to develop new classes of antibacterial from plants and this paper will highlight some of these opportunities.

References: [1] Migliori, G.B. et al. (2007) Eur. Respir. 29: 423–427. [2] Gibbons, S. (2004) Nat. Prod. Rep. 21: 263–277. [3] Smith, E.C.J. et al. (2007) Phytochemistry 68: 210–217.