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Current status of bacterial resistance to third-generation cephalosporins.

A review of the evolution of bacterial resistance to third-generation cephalosporins is presented, focusing mainly on the prototypical member of this group-cefotaxime. Third-generation cephalosporins generally remain highly active against most Enterobacteriaceae, staphylococci, streptococci, Haemophilus, and Neisseriaceae. Only enterobacteria with a high frequency of mutant derepressed strains that hyperproduce chromosomally mediated beta-lactamase, Pseudomonas spp., and some glucose nonfermenter Gram-negative bacilli have demonstrated increased levels of resistance. The significance of derepressed strains and of the recently described extended-spectrum, plasmid-mediated beta-lactamases to the usefulness of the third-generation cephalosporins is discussed.

Cefotaxime↗

Hydrodynamics of bacterial colonies: a model.

We propose a hydrodynamic model for the evolution of bacterial colonies growing on soft agar plates. This model consists of reaction-diffusion equations for the concentrations of nutrients, water, and bacteria, coupled to a single hydrodynamic equation for the velocity field of the bacteria-water mixture. It captures the dynamics inside the colony as well as on its boundary and allows us to identify a mechanism for collective motion towards fresh nutrients, which, in its modeling aspects, is similar to classical chemotaxis. As shown in numerical simulations, our model reproduces both usual colony shapes and typical hydrodynamic motions, such as the whirls and jets recently observed in wet colonies of Bacillus subtilis. The approach presented here could be extended to different experimental situations and provides a general framework for the use of advection-reaction-diffusion equations in modeling bacterial colonies.

Agar↗

Base composition skews, replication orientation, and gene orientation in 12 prokaryote genomes.

Variation in GC content, GC skew and AT skew along genomic regions was examined at third codon positions in completely sequenced prokaryotes. Eight out of nine eubacteria studied show GC and AT skews that change sign at the origin of replication. The leading strand in DNA replication is G-T rich at codon position 3 in six eubacteria, but C-T rich in two Mycoplasma species. In M. genitalium the AT and GC skews are symmetrical around the origin and terminus of replication, whereas its GC content variation has been shown to have a centre of symmetry elsewhere in the genome. Borrelia burgdorferi and Treponema pallidum show extraordinary extents of base composition skew correlated with direction of DNA replication. Base composition skews measured at third codon positions probably reflect mutational biases, whereas those measured over all bases in a sequence (or at codon positions 1 and 2) can be strongly affected by protein considerations due to the tendency in some bacteria for genes to be transcribed in the same direction that they are replicated. Consequently in some species the direction of skew for total genomic DNA is opposite to that for codon position 3.

Archaea↗

Hydrogenase genes are uncommon and highly conserved in Rhizobium leguminosarum bv. viciae.

A screening for hydrogen uptake (hup) genes in Rhizobium leguminosarum bv. viciae isolates from different locations within Spain identified no Hup+ strains, confirming the scarcity of the Hup trait in R. leguminosarum. However, five new Hup+ strains were isolated from Ni-rich soils from Italy and Germany. The hup gene variability was studied in these strains and in six available strains isolated from North America. Sequence analysis of three regions within the hup cluster showed an unusually high conservation among strains, with only 0.5-0.6% polymorphic sites, suggesting that R. leguminosarum acquired hup genes de novo in a very recent event.

Base Sequence↗

Evolution of a degradative bacterial consortium during the enrichment of naphtha solvent.

A microbial mixed culture able to degrade naphtha solvent, a model of hydrocarbon aromatic mixture, was isolated from a hydrocarbon-polluted soil. Composition of the population was monitored by phenotypic and molecular methods applied on soil DNA, on whole enrichment culture DNA, and on 85 isolated strains. Strains were characterized for their 16S rDNA restriction profiles and for their random amplified polymorphic DNA profiles. Catabolic capabilities were monitored by phenotypic traits and by PCR assays for the presence of the catabolic genes methyl mono-oxygenase ( xylA, M), catechol 2,3 dioxygenase (xylE) and toluene dioxygenase (todC1) of TOL and TOD pathways. Different haplotypes belonging to Pseudomonas putida, Ps. aureofaciens and Ps. aeruginosa were found to degrade aromatic compounds and naphtha solvent. The intrinsic catabolic activity of the microbial population of the polluted site was detected by PCR amplification of the xylE gene directly from soil DNA.

Bacteria↗

Ecologic genomics of DNA: upstream bending in prokaryotic promoters.

After our analysis of the distribution of predicted intrinsic curvature along all available complete prokaryotic genomes, the genomes were divided into two groups. Curvature distribution in all prokaryotes of the first group indicated a substantial fraction of promoters characterized by intrinsic DNA curvature located within or upstream of the promoter region. We did not find this peculiar DNA curvature distribution in prokaryotes in the second group. Remarkably, all bacteria of the first group were mesophilic, whereas many prokaryotes of the second group were hyperthermophilic. We hypothesize that DNA curvature plays a biologic role in gene regulation in mesophilic as opposed to hyperthermophilic prokaryotes, i.e., DNA curvature presumably has a functional adaptive significance determined by temperature selection.

5' Untranslated Regions↗

A role for bacteriophages in the evolution and transfer of bacterial virulence determinants.

A virulence-associated region in the genome of Dichelobacter nodosus has been shown to contain an integrase gene which is highly related to the integrases of Shigella flexneri phage Sf6 and coliphages P4 and phi R73, together with open reading frames (vapB, C and D) related to genes borne on plasmids in Neisseria gonorrhoeae, Escherichia coli, Actinobacillus actinomycetemcomitans and Treponema denticola. Similar to P4 and phi R73, the vap region is bracketed by putative bacteriophage att sites and is adjacent to a tRNA gene, which suggests that the vap region has been derived by the integration of a bacteriophage, or a plasmid carrying a bacteriophage-related integrase gene. Many similarities in genes and genes clusters encoding virulence determinants have been found in distantly related bacteria. These genes are often located on plasmids in one organism but on the chromosome in others, implying that transmission of the genes has been followed by integration. Thus, the events which have generated the vap regions of D. nodosus may represent a common mechanism for transfer of virulence determinants. A number of genes involved in the virulence of bacterial pathogens are found on integrated bacteriophages, and we suggest that others will prove to be associated with tRNA genes and/or integrase genes derived from bacteriophages. The use of tRNA genes as integration sites for many bacteriophages and plasmids may favour intergeneric transmission, as tRNA genes are highly conserved.

Attachment Sites, Microbiological↗

Succession of bacterial community composition over two consecutive years in two aquatic systems: a natural lake and a lake-reservoir.

The succession in bacterial community composition was studied over two years in the epilimnion and hypolimnion of two freshwater systems: a natural lake (Pavin Lake) and a lake-reservoir (Sep Reservoir). The bacterial community composition was determined by cloning-sequencing of 16S rRNA and by terminal restriction fragment length polymorphism. Despite large hydrogeological differences, in the Sep Reservoir and Pavin Lake the dominant bacteria were from the same taxonomic divisions, particularly Actinobacteria and Betaproteobacteria. In both ecosystems, these major bacterial divisions showed temporal fluctuations that were much less marked than those occurring at a finer phylogenetic scale. Nutrient availability and mortality factors, the nature of which differed from one lake to another, covaried with the temporal variations in the bacterial community composition at all sampling depths, whereas factors related to seasonal forces (temperature and outflow for Sep Reservoir) seemed to account only for the variation of the hypolimnion bacterial community composition. No seasonal reproducibility in temporal evolution of bacterial community from one year to the next was observed.

Acinetobacter↗

Evolutionary changes of the flhDC flagellar master operon in Shigella strains.

Shigella strains are nonmotile. The master operon of flagellar synthesis, flhDC, was analyzed for genetic damage in 46 Shigella strains representing all known serotypes. In 11 strains (B1, B3, B6, B8, B10, B18, D5, F1B, D10, F3A, and F3C) the flhDC operon was completely deleted. PCR and sequence analysis of the flhDC region of the remaining 35 strains revealed many insertions or deletions associated with insertion sequences, and the majority of the strains were found to be defective in their flhDC genes. As these genes also play a role in regulation of non-flagellar genes, the loss may have other consequences or be driven by selection pressures other than those against flagellar motility. It has been suggested that Shigella strains fall mostly into three clusters within Escherichia coli, with five outlier strains, four of which are also within E. coli (G. M. Pupo, R. Lan, and P. R. Reeves, Proc. Natl. Acad. Sci. USA 97:10567-10572, 2000). The distribution of genetic changes in the flhDC region correlated very well with the three clusters and outlier strains found using housekeeping gene DNA sequences, enabling us to follow the sequence of mutational change in the flhDC locus. Two cluster 2 strains were found to have unique flhDC sequences, which are most probably due to recombination during the exchange of the adjacent O-antigen gene clusters.

Base Sequence↗

Hyperinvasive neonatal group B streptococcus has arisen from a bovine ancestor.

The genetic relatedness and evolutionary relationships between group B streptococcus (GBS) isolates from humans and those from bovines were investigated by phylogenetic analysis of multilocus sequence typing data. The collection of isolates consisted of 111 GBS isolates from cows with mastitis and a diverse global collection of GBS isolates from patients with invasive disease (n = 83) and carriers (n = 69). Cluster analysis showed that the majority of the bovine isolates (93%) grouped into one phylogenetic cluster. The human isolates showed greater diversity and clustered separately from the bovine population. However, the homogeneous human sequence type 17 (ST-17) complex, known to be significantly associated with invasive neonatal disease, was the only human lineage found to be clustered within the bovine population and was distinct from all the other human lineages. Split decomposition analysis revealed that the human isolate ST-17 complex, the major hyperinvasive neonatal clone, has recently arisen from a bovine lineage.

Animals↗

Population dynamics of tuberculosis treatment: mathematical models of the roles of non-compliance and bacterial heterogeneity in the evolution of drug resistance.

SETTING: Patient non-compliance and/or spatial heterogeneity in drug concentration or effectiveness may contribute to the emergence of drug resistance during multiple-drug chemotherapy of tuberculosis. OBJECTIVE: Using mathematical models of mycobacterial population dynamics under antimicrobial treatment, to assess the effects of non-compliance, heterogeneity and other factors on the success of treatment. DESIGN: A mathematical model is used to generate predictions about the ascent of drug resistance in treated hosts with non-compliance and/or a 'protected compartment' of bacteria where only one drug is active; simulations of a more realistic version of this model take into account random mutation, and different assumptions about the size of, and growth rate of bacteria in, the protected compartment. RESULTS: The existence of a protected compartment can increase the likelihood of resistance to the single drug active in that compartment, but only if bacteria resistant to that drug can grow in the protected compartment or if the host is non-adherent to the treatment regimen. However, the protected compartment may also slow the ascent of bacteria resistant to drugs not active in it (e.g. isoniazid) by providing a reservoir of non-selected mycobacteria. The model predicts that relative rates of killing are more important than mutation rates in determining the order in which resistant mutants ascend. Model predictions, in combination with data about drug resistance patterns, suggest that non-compliance, but not heterogeneity, is an important cause of treatment failure. CONCLUSION: Patterns of acquired drug resistance may be used to infer processes of selection during treatment; mathematical models can aid in generating predictions about the relative impacts of treatment parameters in the evolution of resistance, and eventually in suggesting improved treatment protocols.

Antitubercular Agents↗

Repetitive DNA, genome system architecture and genome reorganization.

Repetitive DNA elements are major organizational components of the genome involved in replication, in transmission to daughter cells, and controlling expression of genomic coding sequences. Repetitive elements format the genome system architecture characteristic of each taxonomic group. Appreciating the functional significance of repetitive DNA provides new concepts of genome organization and genome reorganization in evolution.

Adaptation, Biological↗

Gene fusion/fission is a major contributor to evolution of multi-domain bacterial proteins.

Most proteins comprise one or several domains. New domain architectures can be created by combining previously existing domains. The elementary events that create new domain architectures may be categorized into three classes, namely domain(s) insertion or deletion (indel), exchange and repetition. Using 'DomainTeam', a tool dedicated to the search for microsyntenies of domains, we quantified the relative contribution of these events. This tool allowed us to collect homologous bacterial genes encoding proteins that have obviously evolved by modular assembly of domains. We show that indels are the most frequent elementary events and that they occur in most cases at either the N- or C-terminus of the proteins. As revealed by the genomic neighbourhood/context of the corresponding genes, we show that a substantial number of these terminal indels are the consequence of gene fusions/fissions. We provide evidence showing that the contribution of gene fusion/fission to the evolution of multi-domain bacterial proteins is lower-bounded by 27% and upper-bounded by 64%. We conclude that gene fusion/fission is a major contributor to the evolution of multi-domain bacterial proteins.

Bacterial Proteins↗

[Bacterial resistance and management of nosocomial infections: relations to hematology].

Because they receive many infected patients with various degrees of immunosuppression, the haematology departments have a high consumption of antibiotics. The possible relationship between antibiotic consumption and bacterial resistance is discussed in many specialities, especially for some classes like quinolones. This possible relationship has to be evocated in haematology where patients are at high risk of severe sepsis because of neutropenia. In Henri Mondor hospital, we studied the evolution of bacterial susceptibility and of antibiotic consumption in the haematology unit on a 6 year period. We found that this susceptibility was finally stable over time. The main factors which may influence the evolution of the bacterial susceptibility in our study, and in the literature are discussed.

4-Quinolones↗

The complete genomes and proteomes of 27 Staphylococcus aureus bacteriophages.

Bacteriophages are the most abundant life forms in the biosphere. They play important roles in bacterial ecology, evolution, adaptation to new environments, and pathogenesis of human bacterial infections. Here, we report the complete genomic sequences, and predicted proteins of 27 bacteriophages of the Gram-positive bacterium Staphylococcus aureus. Comparative nucleotide and protein sequence analysis indicates that these phages are a remarkable source of untapped genetic diversity, encoding 2,170 predicted protein-encoding ORFs, of which 1,402 cannot be annotated for structure or function, and 522 are proteins with no similarity to other phage or bacterial sequences. Based on their genome size, organization of their gene map and comparative nucleotide and protein sequence analysis, the S. aureus phages can be organized into three groups. Comparison of their gene maps reveals extensive genome mosaicism, hinting to a large reservoir of unidentified S. aureus phage genes. Among the phages in the largest size class (178-214 kbp) that we characterized is phage Twort, the first discovered bacteriophage (responsible for the Twort-D'Herelle effect). These phage genomes offer an exciting opportunity to discern molecular mechanisms of phage evolution and diversity.

Chromosome Mapping↗