Introduction: Microbial Disease; Recent Studies Show That Novel Extracellular Components Can Enhance Microbial Resistance to Lethal Host Chemicals and Increase Virulence

Article excerpt

This volume, in the main, covers a range of topics related to infectious disease caused by organisms which are, at present, or permanently, in the news. Many of these organisms are of substantial public concern, because of major health problems involving them. The article by Basset et al. (1), for example, reviews Helicobacter; who would have believed, 20 years ago, that gastric and duodenal ulcer and possibly gastric cancer, would be linked to the presence of a novel helical bacterium, in the stomach, and no doubt, even fewer would have anticipated the possible involvement of this organism in other diseases. The demonstrated involvement of Helicobacter has enabled clinicians, in some cases, to successfully use antimicrobials to alleviate these conditions. Basset and Holton review factors that influence the occurrence of inflammatory bowel disease, emphasising particularly immunological and bacteriological aspects (2); again, strikingly, there is some evidence for the involvement of Helicobacter spp in such d isorders, although the evidence is much less substantial. Hopefully, further studies will enable these painful and often intransigent disorders to be much more readily alleviated.

The discovery of numerous natural antimicrobial agents, in the thirties, forties and fifties of the last century, and the synthesis of other antimicrobials, led many to believe that the days of lethal infectious diseases, especially those caused by bacteria, were almost over. Even in the earliest days after the discovery of antibiotics, however, resistance was noticed, and a major concern in recent years has been the evolution of numerous antibiotic-resistant organisms; with transferable resistance e.g. by plasmids, as a complication, and with resistance occurring against so many agents, the possible strategies available to the clinician have been greatly reduced. In a few cases, where resistance occurs towards all antibiotics useful against a particular organism, treatment with antibacterials is actually impossible. Stapleton and Taylor write here about antibiotic resistance (3), and their contribution is of considerable value, because their emphasis is on MRSA. MRSA (Methicillin-resistant Staphylococcus aur eus) had become one of the major bacterial problems of the last few years of the 20th century, and will no doubt continue to be a serious clinical problem in the early 21st century, because it is refractory to most, and sometimes all, of the chief agents generally useful against staphylococci. Stapleton and Taylor write cogently, not only about the nature of the resistance, but also about how it may be modulated (3); a number of agents appear able to reduce methicillin resistance of MRSA when they are administered with the antibiotic, and further studies on these agents may offer exciting possibilities for the future. The article of Waugh and Long is also on a "hot" topic in the infectious disease area, one which has become of critical importance because antibiotic resistance has become so widespread, namely on the search for new antibacterials (4). It is obvious from the account given, that there are several ways of approaching this problem. The major approach described in this article, namely gene and enzym e modification, with the use also of novel substrates, has already given some interesting and exciting results and there is clearly further substantial potential (4). The article by Warhurst (5) is in a similar area, in particular on resistance to antifolate drugs and how such resistance can be overcome by the use of novel compounds; what makes this article of even more interest, is that it relates to antimicrobial drug resistance in the malaria parasite. In 1940, D.D. Woods, having established the mode of action of sulphonamides, proposed that agents structurally resembling essential metabolites, should act as antimicrobials. Warhurst's demonstration (5), that we may be able, soon, to design agents which can fit into enzyme active sites, suggests that Woods' vision may soon become reality, and a plethora of new antimicrobials will become available. …