Tackling antibiotic resistance: a dose of common antisense?

Resistance to antimicrobial agents undermines our ability to treat bacterial infections. It attracts intense media and political interest and impacts on personal health and costs to health infrastructures. Bacteria have developed resistance to all licensed antibacterial agents, and their ability to become resistant to unlicensed agents is often demonstrated during the development process. Conventional approaches to antimicrobial development, involving modification of existing agents or production of synthetic derivatives, are unlikely to deliver the range or type of drugs that will be needed to meet all future requirements. Although many companies are seeking novel targets, further radical approaches to both antimicrobial design and the reversal of resistance are now urgently required. In this article, we discuss ‘antisense’ (or ‘antigene’) strategies to inhibit resistance mechanisms at the genetic level. These offer an innovative approach to a global problem and could be used to restore the efficacy of clinically proven agents. Moreover, this strategy has the potential to overcome critical resistances, not only in the so-called ‘superbugs’ (methicillin-resistant Staphylococcus aureus, glycopeptide-resistant enterococci and multidrug-resistant strains of Acinetobacter baumannii, and Pseudomonas aeruginosa), but in resistant strains of any bacterial species.

Heritability of immune function in the caterpillar Spodoptera littoralis

Phenoloxidase (PO) is believed to be a key mediator of immune function in insects and has been implicated both in non-self recognition and in resistance to a variety of parasites and pathogens, including baculoviruses and parasitoids. Using larvae of the Egyptian cotton leafworm, Spodoptera littoralis, we found that despite its apparent importance, haemolymph PO activity varied markedly between individuals, even amongst insects reared under apparently identical conditions. Sib-analysis methods were used to determine whether individuals varied genetically in their PO activity, and hence in one aspect of immune function. The heritability estimate of haemolymph PO activity was high (h 2 = 0.690 +/- 0.069), and PO activity in the haemolymph was strongly correlated with PO activity in both the cuticle and midgut; the sites of entry for most parasites and pathogens. Haemolymph PO activity was also strongly correlated with the degree to which a synthetic parasite (a small piece of nylon monofilament) was encapsulated and melanized (r = 0.622 +/- 0.142), suggesting that the encapsulation response is also heritable. The mechanism maintaining this genetic variation has yet to be elucidated.