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[Current trends in antibacterial chemotherapy (author's transl)].

Antibiotics account for about 15% of world pharmaceutical consumption, but with the rapid development of antibacterial agents capable of reaching most bacterial cell target structures, many bacterial species have become resistant, including S. pneumoniae, H. influenzae and N. gonorrhoeae, which until recently had remained susceptible to penicillin. Moreover, intrinsically resistant species have been selected and are now responsible for nosocomial infections. These shortcomings of chemotherapy, as well as the toxicity and side-effects of a number of drugs, have prompted a search for antibiotics with wider spectrum, lesser sensitivity to bacterial enzymes, reduced toxicity and improved pharmacokinetic properties. During the last 20 years, attempts to extract new antibiotics from natural sources have met with little success, but considerable progress has been achieved in the hemisynthesis of known molecules, such as 6-aminopenicillanic acid or 7-aminocephalosporanic acid, and various changes in these molecules have yielded a variety of new beta-lactam compounds, some of which being still under study and other in clinical use. Changes in the original aminoglycoside molecules have also produced compounds that are less toxic and less susceptible to inactivating enzymes. Among macrolides and sulfonamides, recent developments, although limited, have led to new products or to synergistic combinations. Finally, the search for new compounds which would inhibit two successive steps in the bacterial metabolic pathways constitutes a modern, rational and promising approach to antibacterial chemotherapy.

Aminoglycosides↗

The bacterial flagellum and flagellar motor: structure, assembly and function.

The bacterial flagellum is a complex multicomponent structure which serves as the propulsive organelle for many species of bacteria. Rotation of the helical flagellar filament, driven by a proton-powered motor embedded in the cell wall, enables the flagellum to function as a screw propeller. It seems likely that almost all of the genes required for flagellar formation and function have been identified. Continuing analysis of the portions of the genome containing these genes may reveal the existence of a few more. Transcription of the flagellar genes is under the control of the products of a single operon, and so these genes constitute a regulon. Other controls, both transcriptional and post-transcriptional, have been identified. Many of these genes have been sequenced, and the information obtained will aid in the design of experiments to clarify the various regulatory mechanisms of the flagellar regulon. The flagellum is composed of several substructures. The long helical filament is connected via the flexible hook to the complex basal body which is located in the cell wall. The filament is composed of many copies of a single protein, and can adopt a number of distinct helical forms. Structural analyses of the filament are adding to our understanding of this dynamic polymer. The component proteins of the hook and filament have all been identified. Continuing studies on the structure of the basal body have revealed the presence of several hitherto unknown basal-body proteins, whose identities and functions have yet to be elucidated. The proteins essential for energizing the motor, the Mot and switch proteins, are thought to exist as multisubunit complexes peripheral to the basal body. These complexes have yet to be identified biochemically or morphologically. Not surprisingly, flagellar assembly is a complex process, occurring in several stages. Assembly occurs in a proximal-to-distal fashion; the basal body is assembled before the hook, and the hook before the filament. This pattern is also maintained within the filament, with monomers added at the distal end of the polymer; the same is presumably true of the other axial components. An exception to this general pattern is assembly of the Mot proteins into the motor, which appears to be possible at any time during flagellar assembly. With the identification of the genes encoding many of the flagellar proteins, the roles of these proteins in assembly is understood, but the function of a number of gene products in flagellar formation remains unknown.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗

A geostatistical analysis of small-scale spatial variability in bacterial abundance and community structure in salt marsh creek bank sediments.

Small-scale variations in bacterial abundance and community structure were examined in salt marsh sediments from Virginia's eastern shore. Samples were collected at 5 cm intervals (horizontally) along a 50 cm elevation gradient, over a 215 cm horizontal transect. For each sample, bacterial abundance was determined using acridine orange direct counts and community structure was analyzed using randomly amplified polymorphic DNA fingerprinting of whole-community DNA extracts. A geostatistical analysis was used to determine the degree of spatial autocorrelation among the samples, for each variable and each direction (horizontal and vertical). The proportion of variance in bacterial abundance that could be accounted for by the spatial model was quite high (vertical: 60%, horizontal: 73%); significant autocorrelation was found among samples separated by 25 cm in the vertical direction and up to 115 cm horizontally. In contrast, most of the variability in community structure was not accounted for by simply considering the spatial separation of samples (vertical: 11%, horizontal: 22%), and must reflect variability from other parameters (e.g., variation at other spatial scales, experimental error, or environmental heterogeneity). Microbial community patch size based upon overall similarity in community structure varied between 17 cm (vertical) and 35 cm (horizontal). Overall, variability due to horizontal position (distance from the creek bank) was much smaller than that due to vertical position (elevation) for both community properties assayed. This suggests that processes more correlated with elevation (e.g., drainage and redox potential) vary at a smaller scale (therefore producing smaller patch sizes) than processes controlled by distance from the creek bank.

Bacteria↗

Bacterial diversity and community structure in an aerated lagoon revealed by ribosomal intergenic spacer analyses and 16S ribosomal DNA sequencing.

We investigated the bacterial community structure in an aerated plug-flow lagoon treating pulp and paper mill effluent. For this investigation, we developed a composite method based on analyses of PCR amplicons containing the ribosomal intergenic spacer (RIS) and its flanking partial 16S rRNA gene. Community percent similarity was determined on the basis of RIS length polymorphism. A community succession was evident in the lagoon, indicated by a progressive community transition through seven sample locations. The most abrupt changes in community structure were associated with a temperature change from 39 to 35 degrees C and with increases in dissolved oxygen. The temporal differences in community structure, based on summer and winter samplings, were greater than the spatial differences during either season. Clone libraries of rDNA-RIS amplicons were constructed from each of three summer samples. Among 90 clones analyzed (30 clones from each sample), 56 phylotypes were distinguished by restriction fragment length polymorphism. Indices of phylotype richness, evenness, and diversity all increased in clone libraries from the beginning to the end of the lagoon. A representative clone of each phylotype was phylogenetically analyzed on the basis of its partial 16S rRNA gene sequence (ca. 450 bp). Phylogenetic analysis confirmed the increase in diversity and further indicated increasing richness of bacterial divisions. Pioneers in the community spatial succession appeared to include thermotolerant, microaerophilic methanol-oxidizing bacteria related to the genus Methylobacillus, as well as thermotolerant, microaerophilic nitrogen-fixing bacteria related to the genus Azospirillum.

Bacteria↗

[Structure and functions of bacterial proteinase precursors].

The data on the precursors of bacterial proteases were generalized. The structure and special features of processing of the precursors of bacillary subtilisins, the alpha-lytic protease from Lysobacter enzymogenes and the related chymotrypsin-like proteases from Streptomyces griseus, and the metalloproteases from bacilli and Pseudomonas aeruginosa were discussed. The approaches to producing the precursors and the protease propeptides and to in vitro characterizing them were particularly analyzed. The following physiological functions of the propeptides within the protease precursors were considered probable: (a) inhibition of the proteases to protect the host cells from the proteolytic damage; (b) participation in the folding of the mature enzyme; and (c) providing for the protease interaction with the bacterial cell surveillance mechanisms, including protease translocation through the cell wall.

Amino Acid Sequence↗

Does disturbance and restoration of alpine grassland soils affect the genetic structure and diversity of bacterial and N2-fixing populations?

Responses of bacterial communities to disturbance and restoration processes were investigated on alpine grassland soil. Bulk soil, rhizosphere soil and two soil separates, i.e. sand-size (2000-200 microm) and silt-size (50-2 microm) were sampled from undisturbed grassland soil to soil under restoration for 1 month, 1 year, 4 years and 13 years after disturbance. Automated ribosomal intergenic spacer analysis (ARISA) and restriction fragment length polymorphism (RFLP) of nifH gene pools were used to assay genetic structure of the bacterial communities and N2-fixing guild. According to the distribution of ARISA band length in bacterial phyla, the dominance of ARISA bands below 400 bp showed that Gram-positive bacteria would be predominant in the studied grassland soil when not disturbed. Disturbance affected the genetic structure of bacterial community and of N2-fixing guild in relation to their location within the selected habitats. Shifts in IGS and nifH profiles of bulk soil metagenome were larger than those observed from sand-size- and silt-size-fractions, accounting for 40-50% of the variance in the profiles. Restoration of the genetic structure of telluric bacteria community and N2-fixing populations was found to be influenced by the spatial heterogeneity of the soil and niche diversification. Particular bacterial genetic structure within distinct habitats were evidenced and must be defined as subdivisions of the meta-community of bulk soil. Scale of soil microbial diversity/stability relationships is discussed with special attention to disconnected bacterial habitat compared with whole soil with multiple niches.

Bacteria↗

Bacterial protein kinases that recognize tertiary rather than primary structure?

While all characterized eukaryotic protein kinases that phosphorylate hydroxy aminoacyl residues in proteins recognize primary structure, certain bacterial protein kinases are proving to recognize tertiary structure. It is proposed that these latter enzymes evolved independently of the superfamily of the former protein kinases and that their modes of target protein recognition and action are entirely different.

Gram-Positive Bacteria↗