Toward Virulence Inhibition: Beyond Cell Wall.

(Mtb) is one of the most successful bacterial pathogens in human history. Even in the antibiotic era, Mtb is widespread and causes millions of new cases of tuberculosis each year. The ability to disrupt the host's innate and adaptive immunity, as well as natural persistence, complicates disease control.

The Benefits of Toxicity: VapBC TA Module Is Induced by Tetracycline Exposure and Promotes Survival.

Toxin-antitoxin (TA) systems are widely present in bacterial genomes. , a common model organism for studying physiology, has eight TA loci, including and . This study aims to investigate the physiological significance of these TA systems.

Development of Heterologous Expression System and Optimization of the Method of Cholera Toxin β-Subunit Production in E. coli.

Cholera is a deadly infection disease, which is usually associated with low hygiene levels and limited access to high-quality drinking water. An effective way to prevent cholera is the use of vaccines. Among active vaccine components there is the CtxB protein (cholera toxin β-subunit).

VapC toxin switches M. smegmatis cells into dormancy through 23S rRNA cleavage.

Mycobacterium tuberculosis is an extremely successful pathogen known for its ability to cause latent infection. The latter is connected with the bacterium resting state development and is considered to be based on the activity of toxin-antitoxin (TA) systems at least in part. Here we studied the physiological and proteomic consequences of VapC toxin overexpression together with the features of the protein synthesis apparatus and compared them with the characteristics of dormant mycobacterial cells in an M.

Cadaverine biosynthesis contributes to decreased Escherichia coli susceptibility to antibiotics.

Some bacterial stress responses are involved in survival under antibiotic treatment and contribute to less susceptible microbial forms selection. Here, we tested the role of cadaverine, one of the biogenic polyamines considered as universal adaptogens, in the processes. The expression of ldcC and cadA genes, encoding cadaverine-producing lysine decarboxylase, increased in Escherichia coli cells exposed to β-lactams and fluoroquinolones but not aminoglycosides.

possesses operational agmatinase but contains no detectable polyamines.

Background: Polyamines are widespread intracellular molecules able to influence antibiotic susceptibility, but almost nothing is known on their occurrence and physiological role in mycobacteria.

Methods: here, we analyzed transcriptomic, proteomic and biochemical data and obtained the first evidence for the post-transcriptional expression of some genes attributed to polyamine metabolism and polyamine transport in Mycolicibacterium smegmatis (basionym Mycobacterium smegmatis).

Results: in our experiments, exponentially growing cells demonstrated transcription of 21 polyamine-associated genes and possessed 7 enzymes of polyamine metabolism and 2 polyamine transport proteins.

Stationary-phase genes upregulated by polyamines are responsible for the formation of Escherichia coli persister cells tolerant to netilmicin.

Persisters are rare phenotypic variants of regular bacterial cells that survive lethal antibiotics or stresses owing to slowing down of their metabolism. Recently, we have shown that polyamine putrescine can upregulate persister cell formation in Escherichia coli via the stimulation of rpoS expression, encoding a master regulator of general stress response. We hypothesized that rmf and yqjD, the stationary-phase genes responsible for ribosome inactivation, might be good candidates for the similar role owing to their involvement in translational arrest and the ability to be affected by polyamines.

Putrescine controls the formation of Escherichia coli persister cells tolerant to aminoglycoside netilmicin.

Persisters are suggested to be the products of a phenotypic variability that are quasi-dormant forms of regular bacterial cells highly tolerant to antibiotics. Our previous investigations revealed that a decrease in antibiotic tolerance of Escherichia coli cells could be reached through the inhibition of key enzymes of polyamine synthesis (putrescine, spermidine). We therefore assumed that polyamines could be involved in persister cell formation.

Polyamines reduce oxidative stress in Escherichia coli cells exposed to bactericidal antibiotics.

Bactericidal antibiotics (fluoroquinolones, aminoglycosides and cephalosporins) at their sublethal concentrations were able to produce hydroxyl radicals, hydrogen peroxide and superoxide anions (ROS) in Escherichia coli cells, which resulted in damage to proteins and DNA. The cells responded to oxidative stress by a 2-3-fold increase in cell polyamines (putrescine, spermidine) produced as a consequence of upregulation of ornithine decarboxylase (ODC). Relief of oxidative stress by cessation of culture aeration or addition of antioxidants substantially diminished or even completely abolished polyamine accumulation observed in response to antibiotics.