Molecular basis of bacterial outer membrane permeability revisited

Gram-negative bacteria characteristically are surrounded by an outer membrane (OM). Analysis of prokaryote phylogeny using signature sequences in proteins even led to the notion that a major phylogenetic division exists between organisms with double-membrane envelopes (diderms) and those with only a simple cytoplasmic membrane (monoderms) (240). It is likely that the most important function for the additional membrane layer, the OM, in gram-negative bacteria is to serve as a selective permeation barrier. My earlier review of this subject, written with Martti Vaara, appeared in 1985 (464). It was an opportune time for such a review because the fundamental properties of the Escherichia coli porins and the specific maltodextrin channel, LamB, were characterized a few years earlier (see, for example, references 388 and 460-462) and the asymmetric structure of the OM bilayer, with lipopolysaccharides (LPS) located exclusively in the outer leaflet (316), offered an explanation for the unusually slow influx of lipophilic solutes. In the intervening 18 years, explosive progress has occurred in the field. Diffusion through the nonspecific porin channels and the specific channels are now understood in molecular detail, thanks to the elucidation of the crystal structure of these proteins. Channel proteins were identified in many nonenteric bacteria as a result of the rapid growth of our knowledge of the genome sequences, and in some cases this has offered insights into the physiology of various organisms in their native habitat. Studies of LPS not only showed us the impressive diversity of LPS structures in the bacterial kingdom but also led to the realization that the LPS structure may be modified in response to the conditions prevailing in the environment. The present review attempts to summarize the development in the field since 1985. The major problem in presenting the results has been the information explosion. For example, more than 650 articles with the word porin in the title have been published during this period. If the databases are searched with porin or lipopolysaccharide as keywords, literally thousands of references are retrieved. Therefore, I had to be severely restrictive with citations in order to keep the review within a reasonable (and perhaps useful) size. I tried to limit the discussion strictly to selective permeability, eliminating most papers dealing with the biosynthesis and assembly of the OM or with the role of the OM in the interaction of bacteria with the environment, including higher animals and plants. I also apologize at the outset for the omission of many references which were not cited because the main message could be found in other articles or reviews or, probably most frequently, because of my oversight.