Bacterial Therapy of Cancer: A Way to the Dustbin of History or to the Medicine of the Future?

Bacteria are the constant companions of the human body throughout its life and even after its death. The history of a human disease such as cancer and the history of microorganisms, particularly bacteria, are believed to closely intertwined. This review was conceived to highlight the attempts of scientists from ancient times to the present day to discover the relationship between bacteria and the emergence or development of tumors in the human body. Challenges and achievements of 21st century science in forcing bacteria to serve for cancer treatment are considered. The future possibilities of bacterial cancer therapy, including the creation of bacterial microrobots, or "bacteriobots", are also discussed.

Contact-Dependent Growth Inhibition in Bacteria: Do Not Get Too Close!

Over millions of years of evolution, bacteria have developed complex strategies for intra-and interspecies interactions and competition for ecological niches and resources. Contact-dependent growth inhibition systems (CDI) are designed to realize a direct physical contact of one bacterial cell with other cells in proximity via receptor-mediated toxin delivery. These systems are found in many microorganisms including clinically important human pathogens. The main purpose of these systems is to provide competitive advantages for the growth of the population. In addition, non-competitive roles for CDI toxin delivery systems including interbacterial signal transduction and mediators of bacterial collaboration have been suggested. In this review, our goal was to systematize the recent findings on the structure, mechanisms, and purpose of CDI systems in bacterial populations and discuss the potential biological and evolutionary impact of CDI-mediated interbacterial competition and/or cooperation.

Plant Secondary Metabolites in the Battle of Drugs and Drug-Resistant Bacteria: New Heroes or Worse Clones of Antibiotics?

Infectious diseases that are caused by bacteria are an important cause of mortality and morbidity in all regions of the world. Bacterial drug resistance has grown in the last decades, but the rate of discovery of new antibiotics has steadily decreased. Therefore, the search for new effective antibacterial agents has become a top priority. The plant kingdom seems to be a deep well for searching for novel antimicrobial agents. This is due to the many attractive features of plants: they are readily available and cheap, extracts or compounds from plant sources often demonstrate high-level activity against pathogens, and they rarely have severe side effects. The huge variety of plant-derived compounds provides very diverse chemical structures that may supply both the novel mechanisms of antimicrobial action and provide us with new targets within the bacterial cell. In addition, the rapid development of modern biotechnologies opens up the way for obtaining bioactive compounds in environmentally friendly and low-toxic conditions. In this short review, we ask the question: do antibacterial agents derived from plants have a chance to become a panacea against infectious diseases in the "post-antibiotics era".

Harnessing the Potential of Killers and Altruists within the Microbial Community: A Possible Alternative to Antibiotic Therapy?

In the context of a post-antibiotic era, the phenomenon of microbial allolysis, which is defined as the partial killing of bacterial population induced by other cells of the same species, may take on greater significance. This phenomenon was revealed in some bacterial species such as Streptococcus pneumoniae and Bacillus subtilis, and has been suspected to occur in some other species or genera, such as enterococci. The mechanisms of this phenomenon, as well as its role in the life of microbial populations still form part of ongoing research. Herein, we describe recent developments in allolysis in the context of its practical benefits as a form of cell death that may give rise to developing new strategies for manipulating the life and death of bacterial communities. We highlight how such findings may be viewed with importance and potential within the fields of medicine, biotechnology, and pharmacology.

Mass-spectrometry based minisequencing method for the rapid detection of drug resistance in Mycobacterium tuberculosis.

A MALDI TOF MS based minisequencing method has been developed and applied for the analysis of rifampin (RIF)- and isoniazid (INH)-resistant M. tuberculosis strains. Eight genetic markers of RIF resistance-nucleotide polymorphisms located in RRDR of rpoB gene, and three of INH resistance including codon 315 of katG gene and -8 and -15 positions of the promoter region of fabG1-inhA operon were worked out. Based on the analysis of 100 M. tuberculosis strains collected from the Moscow region in 1997-2005 we deduced that 91% of RIF-resistant and 94% of INH-resistant strains can be identified using the technique suggested. The approach is rapid, reliable and allows to reveal the drug resistance of M. tuberculosis strains within 12 h after sample isolation.

Comparative genomic analysis of Mycobacterium tuberculosis drug resistant strains from Russia.

Tuberculosis caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (MTB) strains is a growing problem in many countries. The availability of the complete nucleotide sequences of several MTB genomes allows to use the comparative genomics as a tool to study the relationships of strains and differences in their evolutionary history including acquisition of drug-resistance. In our work, we sequenced three genomes of Russian MTB strains of different phenotypes--drug susceptible, MDR and XDR. Of them, MDR and XDR strains were collected in Tomsk (Siberia, Russia) during the local TB outbreak in 1998-1999 and belonged to rare KQ and KY families in accordance with IS6110 typing, which are considered endemic for Russia. Based on phylogenetic analysis, our isolates belonged to different genetic families, Beijing, Ural and LAM, which made the direct comparison of their genomes impossible. For this reason we performed their comparison in the broader context of all M. tuberculosis genomes available in GenBank. The list of unique individual non-synonymous SNPs for each sequenced isolate was formed by comparison with all SNPs detected within the same phylogenetic group. For further functional analysis, all proteins with unique SNPs were ascribed to 20 different functional classes based on Clusters of Orthologous Groups (COG). We have confirmed drug resistant status of our isolates that harbored almost all known drug-resistance associated mutations. Unique SNPs of an XDR isolate CTRI-4(XDR), belonging to a Beijing family were compared in more detail with SNPs of additional 14 Russian XDR strains of the same family. Only type specific mutations in genes of repair, replication and recombination system (COG category L) were found common within this group. Probably the other unique SNPs discovered in CTRI-4(XDR) may have an important role in adaptation of this microorganism to its surrounding and in escape from antituberculosis drugs treatment.

Comparative evaluation of new typing schemes for urogenital Chlamydia trachomatis isolates.

Thirty urogenital Chlamydia trachomatis isolates collected in Moscow in 2005 were typed using newly developed molecular typing approaches: (1) multilocus sequence typing (MLST(7)) based on sequences of seven housekeeping genes (http://pubmlst.org/chlamydiales/), (2) MLST(5) based on the investigation of five target regions of the chlamydial genome and (3) ompA gene sequencing supplemented with three variable number tandem repeat (VNTR) loci of the genome. ompA typing divided all isolates into 11 groups with E serotype dominating, while MLST7, MLST5 and VNTR analysis divided them into eight, 20 and 18 groups, respectively. The discriminatory power of each method calculated using the Hunter-Gaston discriminatory index was found to be 0.83 for the ompA typing scheme, 0.82 for MLST(7) and 0.95 for MLST(5). A novel sequence type combining 13% of all strains was discovered, as well as new alleles of genes. This is the first study characterizing the genetic diversity of the urogenital C. trachomatis population in Central Russia using MLST. We conclude that the MLST(7) scheme is the best possible choice for global epidemiological purposes, whereas MLST(5) is more appropriate for tracing local outbreaks.

Molecular characteristics of rifampicin- and isoniazid-resistant Mycobacterium tuberculosis isolates from the Russian Federation.

OBJECTIVES: Three Mycobacterium tuberculosis genetic loci--rpoB and katG genes and the fabG1(mabA)-inhA operon promoter region--were studied to reveal the mutations associated with rifampicin and isoniazid resistance. METHODS: Four hundred and twelve isolates of M. tuberculosis from different regions of the Russian Federation were collected during 1997-2005. A matrix-assisted laser-desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS)-based minisequencing method was used for the detection of mutations. RESULTS: Thirteen different variants of single mutations in codons 533, 531, 526, 516, 513 and 511 of the rifampicin resistance-determining region of the rpoB gene as well as the TTG insertion in the 514a position were found among the rifampicin-resistant isolates. Single nucleotide substitutions in codons 531, 526 and 516 (64.8%, 10.3% and 7.7%, respectively) were the most prevalent mutations. Codon 526 was shown to be the most variable of all. No mutations were detected in rpoB genes for 29 (10.7%) of the rifampicin-resistant isolates. 76.9% of the isoniazid-resistant isolates carried single mutations in codon 315 of the katG gene. For another 12.9% of them, double mutations in the katG gene and the fabG1(mabA)-inhA promoter region were revealed. No mutations were detected in 8.2% of the isoniazid-resistant isolates. CONCLUSIONS: Molecular analysis of the loci of rpoB and katG genes and the inhA promoter region of 412 M. tuberculosis clinical isolates from various parts of the Russian Federation was carried out. The new MALDI-TOF MS-based method may be used for rapid and accurate monitoring of the spread of drug resistance.