RESUMO
How do mycobacteria divide? Cell division has been studied extensively in the model rod-shaped bacteria Escherichia coli and Bacillus subtilis, but much less is understood about cell division in mycobacteria, a genus that includes the major human pathogens M. tuberculosis and M. leprae. In general, bacterial cell division requires the concerted effort of many proteins in both space and time to elongate the cell, replicate and segregate the chromosome, and construct and destruct the septum - processes which result in the creation of two new daughter cells. Here, we describe these distinct stages of cell division in B. subtilis and follow with the current knowledge in mycobacteria. As will become apparent, there are many differences between mycobacteria and B. subtilis in terms of both the broad outline of cell division and the molecular details. So, while the fundamental challenge of spatially and temporally organizing cell division is shared between these rod-shaped bacteria, they have solved these challenges in often vastly different ways.
Assuntos
Divisão Celular/fisiologia , Mycobacterium/crescimento & desenvolvimento , Mycobacterium/metabolismo , Bacillus subtilis/genética , Bacillus subtilis/crescimento & desenvolvimento , Bacillus subtilis/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Ciclo Celular/metabolismo , Divisão Celular/genética , Parede Celular , Replicação do DNA , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Mycobacterium/genética , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/metabolismoRESUMO
FtsZ is a widely distributed major cytoskeletal protein involved in the archaea and bacteria cell division. It is the most critical component in the division machinery and similar to tubulin in structure and function. Four major roles of FtsZ have been characterized: cell elongation, GTPase, cell division, and bacterial cytoskeleton. FtsZ subunits can be assembled into protofilaments. Mycobacteria consist of a large family of medical and environmental important bacteria, such as M. leprae, M. tuberculosis, the pathogen of leprosy, and tuberculosis. Structure, function, and regulation of mycobacteria FtsZ are summarized here, together with the implication of FtsZ as potential novel drug target for anti-tuberculosis therapeutics.
Assuntos
Proteínas de Bactérias/genética , Proteínas do Citoesqueleto/genética , Mycobacterium/genética , Sequência de Aminoácidos , Antituberculosos/uso terapêutico , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/fisiologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/genética , Divisão Celular/fisiologia , Proteínas do Citoesqueleto/antagonistas & inibidores , Proteínas do Citoesqueleto/fisiologia , Regulação Bacteriana da Expressão Gênica , Humanos , Dados de Sequência Molecular , Mycobacterium/classificação , Mycobacterium/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Homologia de Sequência de Aminoácidos , Tuberculose/tratamento farmacológico , Tuberculose/microbiologiaRESUMO
We have isolated a UV-induced temperature-sensitive mutant of Mycobacterium smegmatis that fails to grow at 42 degrees C and exhibits a filamentous phenotype following incubation at the nonpermissive temperature, reminiscent of a defect in cell division. Complementation of this mutant with an M. smegmatis genomic library and subsequent subcloning reveal that the defect lies within the M. smegmatis dnaG gene encoding DNA primase. Sequence analysis of the mutant dnaG allele reveals a substitution of proline for alanine at position 496. Thus, dnaG is an essential gene in M. smegmatis, and DNA replication and cell division are coupled processes in this species. Characterization of the sequences flanking the M. smegmatis dnaG gene shows that it is not part of the highly conserved macromolecular synthesis operon present in other eubacterial species but is part of an operon with a dgt gene encoding dGTPase. The organization of this operon is conserved in Mycobacterium tuberculosis and Mycobacterium leprae, suggesting that regulation of DNA replication, transcription, and translation may be coordinated differently in the mycobacteria than in other bacteria.
Assuntos
DNA Primase/genética , Replicação do DNA/genética , Genes Bacterianos/genética , Mycobacterium/genética , Alelos , Sequência de Aminoácidos , Divisão Celular/genética , Análise Mutacional de DNA , Teste de Complementação Genética , Ligação Genética , Dados de Sequência Molecular , Mutação , Mycobacterium/citologia , Fases de Leitura Aberta/genética , Óperon/genética , Mapeamento por Restrição , Homologia de Sequência de Aminoácidos , TemperaturaRESUMO
A continuous 75627 bp segment of the Mycobacterium leprae chromosome spanning the oriC region was sequenced. The gene order at this locus was similar to that found in the replication origin region of many other prokaryotes, particularly Mycobacterium tuberculosis and Streptomyces coelicolor. As in the case of several Gram-positive bacteria, essential genes involved in basic cellular functions, such as DNA or RNA metabolism (dnaA, dnaB, dnaN, gyrB, gyrA, pcnB, recF, rnpA, ssb), cell wall synthesis (ponA, pbpA) and probably cell division (gidB, rodA) were found. Strikingly, the gidA gene was absent from this part of the genome and there was no rRNA operon near oriC. The gyrA gene harbours an intein coding sequence indicating that protein splicing is required to produce the mature A subunit of DNA gyrase. Among the many other noteworthy features were ORFs encoding putative serine/threonine protein kinases and a protein phosphatase, three tRNA genes, one M. leprae-specific repetitive element and a glnQ pseudogene.