Bacterial adhesion: modulation by antibiotics which perturb protein synthesis.

It has been known for a long time that antibiotics are capable of altering bacterial surfaces, resulting in morphological changes that can be detected by electron microscopy (2); however, more subtle alterations at the molecular level may be undetectable at the ultrastructural level. Certain antibiotics disturb the metabolism and processing of bacterial surface components (59, 71), whereas others disorganize the bacterial surface architecture (36, 39). Regardless of the mechanism of action, the induced surface changes can influence the strength of the attractive and repulsive forces responsible for bacterial surface interactions with molecules and cells in the environment. These interactions are important in the early stages of bacterial pathogenesis, that is, attachment to mucosal surfaces and invasion, and perhaps also during subsequent steps of the infectious process (5, 14, 15, 18, 38). Adhesins are ligand molecules that are located on the surfaces of pathogenic bacteria and that endow the organisms with the ability to bind specifically to complementary receptors on the mucosal surfaces of the susceptible host. Many studies have provided evidence that the expression and specific function of adhesins can be affected by concentrations of antibiotics that are unable to completely inhibit bacterial growth in vitro (sub-MICs; reviewed in references 13 and 66). These observations raise the possibility that sub-MICs of antibiotics may prevent the infectious process by inhibiting the mucosal attachment step (8, 64). Although many in vitro experiments have shown an effect of antibiotics on adhesion, only a few have been designed to define the molecular events involved. Because of the complexity of the microbe-drug-host interaction, interpretations concerning the effect of antibiotics on bacterial adhesion have been difficult. In this article, we review this topic, relating the known sites of action of various classes of antibiotics which perturb protein synthesis (31, 71) with what is known about the molecular mechanism of bacterial adhesion. Other antimicrobial agents are reviewed elsewhere (65). The concepts described in this review will be highlighted by examples referring only to the better-characterized adhesin-receptor systems, the paradigm being the type 1 fimbria-mediated adhesion of Escherichia coli to mannosylated receptors on eucaryotic cells. We emphasize technical aspects when necessary to reconcile apparent contradictions between different studies. A synopsis of the reviewed studies is shown in Table 1. The effectiveness of antibiotics that inhibit protein synthe-