MicrobiologyBytes

Bacteria communicate with one another via quorum-sensing signal molecules. This paper describes the first example of quorum-sensing molecules participating in interspecies bacterial cell death. This is an interesting observation in its own right – but think about this: these peptides potentially provide the basis for a new class of antibiotics which trigger death by acting from outside the cell.

Novel Quorum-Sensing Peptides Mediating Interspecies Bacterial Cell Death. (2013) mBio 4(3): e00314-13 doi: 10.1128/mBio.00314-13
Escherichia coli mazEF is a toxin-antitoxin stress-induced module mediating cell death. It requires the quorum-sensing signal (QS) “extracellular death factor” (EDF), the penta-peptide NNWNN (EcEDF), enhancing the endoribonucleolytic activity of E. coli toxin MazF. Here we discovered that E. coli mazEF-mediated cell death could be triggered by QS peptides from the supernatants (SN) of the Gram-positive bacterium Bacillus subtilis and the Gram-negative bacterium Pseudomonas aeruginosa. In the SN of B. subtilis, we found one EDF, the hexapeptide RGQQNE, called BsEDF. In the SN of P. aeruginosa, we found three EDFs: the nonapeptide INEQTVVTK, called PaEDF-1, and two hexadecapeptides, VEVSDDGSGGNTSLSQ, called PaEDF-2, and APKLSDGAAAGYVTKA, called PaEDF-3. When added to a diluted E. coli cultures, each of these peptides acted as an interspecies EDF that triggered mazEF-mediated death. Furthermore, though their sequences are very different, each of these EDFs amplified the endoribonucleolytic activity of E. coli MazF, probably by interacting with different sites on E. coli MazF. Finally, we suggest that EDFs may become the basis for a new class of antibiotics that trigger death from outside the bacterial cells.

Microbiology Today: Getting the message out

The Society for General Microbiology (SGM) leads the way on antimicrobial resistance.

http://www.sgm.ac.uk/en/publications/microbiology-today/current-issue.cfm

Alternatives to antibiotics are urgently needed in animal agriculture. The form these alternatives should take presents a complex problem due to the various uses of antibiotics in animal agriculture, including disease treatment, disease prevention, and growth promotion, and to the relative contribution of these uses to the antibiotic resistance problem. Numerous antibiotic alternatives, such as pre- and probiotics, have been proposed but show variable success. This is because a fundamental understanding of how antibiotics improve feed efficiency is lacking, and because an individual alternative is unlikely to embody all of the performance-enhancing functions of antibiotics. High-throughput technologies need to be applied to better understand the problem, and informed combinations of alternatives, including vaccines, need to be considered.

This article discusses alternative approaches to animal (and therefore human) health, such as:

• Feed additives such as pre- and probiotics
• Phage therapy
• Vaccines
• Mixing additives: potentiated probiotics and synbiotics

Treatment, promotion, commotion: antibiotic alternatives in food-producing animals. (2013) Trends Microbiol. 21(3): 114-119. doi: 10.1016/j.tim.2012.11.001

Solutions are urgently required for the growing number of infections caused by antibiotic-resistant bacteria. Bacteriocins, which are antimicrobial peptides produced by certain bacteria, might warrant serious consideration as alternatives to traditional antibiotics. These molecules exhibit significant potency against other bacteria (including antibiotic-resistant strains), are stable and can have narrow or broad activity spectra. Bacteriocins can even be produced in situ in the gut by probiotic bacteria to combat intestinal infections. Although the application of specific bacteriocins might be curtailed by the development of resistance, an understanding of the mechanisms by which such resistance could emerge will enable researchers to develop strategies to minimize this potential problem.

Bacteriocins – a viable alternative to antibiotics? (2013) Nat Rev Microbiol. 11(2): 95-105. doi: 10.1038/nrmicro2937

The world is starting to win the war against tuberculosis, but drug-resistant forms pose a new threat.
Nature News: http://goo.gl/Ua9c8

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Latest Edition – Antimicrobials

• Antibiotic discovery: then and now
• Accessing the biosynthetic potential of Actinobacteria
• Waging war on fungi – the unknown superbugs
• Enzybiotics and phages: safe alternatives to antibiotics in the control of food safety
• Drugs from bugs that kill bugs
• Comment: Antibiotic Action
• and more

The growth and success of bacterial populations depends upon the production of extracellular factors that are secreted to perform many functions such as nutrient acquisition, protection from the environment and the creation of enemy-free space. These factors provide a benefit to the local population of cells, and so their production is potentially vulnerable to exploitation by ‘cheats’ that avoid the cost of producing them, while benefiting from those produced by others. This problem, sometimes referred to as the ‘public goods dilemma’, is general to all biological populations where cooperation enhances population fitness, because while a group of individuals would benefit from cooperation, cooperation may not be stable if individuals can gain from pursuing their own selfish interests.

This paper argues that conflict over public goods reduces population fitness in bacterial biofilms, and that this effect is greater than in planktonic populations. it goes on to discuss the clinical implications that arise from altering the susceptibility to antibiotics.

Quorum-sensing and cheating in bacterial biofilms. (2012) Proc. R. Soc. B 279(1748): 4765-4771
The idea from human societies that self-interest can lead to a breakdown of cooperation at the group level is sometimes termed the public goods dilemma. We tested this idea in the opportunistic bacterial pathogen, Pseudomonas aeruginosa, by examining the influence of putative cheats that do not cooperate via cell-to-cell signalling (quorum-sensing, QS). We found that: (i) QS cheating occurs in biofilm populations owing to exploitation of QS-regulated public goods; (ii) the thickness and density of biofilms was reduced by the presence of non-cooperative cheats; (iii) population growth was reduced by the presence of cheats, and this reduction was greater in biofilms than in planktonic populations; (iv) the susceptibility of biofilms to antibiotics was increased by the presence of cheats; and (v) coercing cooperator cells to increase their level of cooperation decreases the extent to which the presence of cheats reduces population productivity. Our results provide clear support that conflict over public goods reduces population fitness in bacterial biofilms, and that this effect is greater than in planktonic populations. Finally, we discuss the clinical implications that arise from altering the susceptibility to antibiotics.

Zinc is an essential trace element for the growth of most organisms. Quantities of zinc inside cells are highly regulated, as too little zinc does not support growth, while too much zinc is toxic. Numerous bacterial cells require zinc uptake systems for growth and virulence. The work presented here demonstrates that the microbiota in the gastrointestinal tract reduces the quantity of zinc. Without a high-affinity zinc transporter, Campylobacter jejuni, a commensal organism of chickens, is unable to replicate or colonize the gastrointestinal tract. This is the first demonstration of zinc competition between microbiota in the gastrointestinal tract of a host. These results could have profound implications in the field of microbial pathogenesis and in our understanding of host metabolism and the microbiota.

Zinc Competition among the Intestinal Microbiota. (2012) mBio 3(4) e00171-12 doi: 10.1128/mBio.00171-12
Bioavailable levels of trace metals, such as iron and zinc, for bacterial growth in nature are sufficiently low that most microbes have evolved high-affinity binding and transport systems. The microbe Campylobacter jejuni lives in the gastrointestinal tract of chickens, the principal source of human infection. A high-affinity ABC transporter for zinc uptake is required for Campylobacter survival in chicken intestines in the presence of a normal microbiota but not when chickens are raised with a limited microbiota. Mass spectrometric analysis of cecal contents revealed the presence of numerous zinc-binding proteins in conventional chicks compared to the number in limited-microbiota chicks. The presence of a microbiota results in the production of host zinc-binding enzymes, causing a growth restriction for bacteria that lack the high-affinity zinc transporter. Such transporters in a wide range of pathogenic bacteria make them good targets for the development of broad-spectrum antimicrobials.

Mycobacterium marinum is a slow-growing mycobacterium with an optimal growth temperature of 30°C. It most frequently causes skin and soft tissue infections in the extremities. Patients typically show clusters of nodules, ulcers, or verrucous plaques that may centripetally spread from the arms or legs in a sporotrichoid pattern – pulmonary infections, osteomyelitis, arthritis, and disseminated diseases are encountered to a lesser extent.

Many factors play important roles in causing M. marinum infections. These include prescription of local or systemic steroids or immunosuppressive agents, and structural lung diseases. Among these, the primary risk factor is exposure to aquatic environments or marine animals. Thus M. marinum infection is also known as “fish tank granuloma”.

Fish Tank Granuloma Caused by Mycobacterium marinum. (2012) PLoS ONE 7(7): e41296. doi:10.1371/journal.pone.0041296
Introduction: Mycobacterium marinum causes skin and soft tissue, bone and joint, and rare disseminated infections. In this study, we aimed to investigate the relationship between treatment outcome and antimicrobial susceptibility patterns. A total of 27 patients with M. marinum infections were enrolled.
Methods: Data on clinical characteristics and therapeutic methods were collected and analyzed. We also determined the minimum inhibitory concentrations of 7 antibiotics against 30 isolates from these patients.
Results: Twenty-seven patients received antimycobacterial agents with or without surgical debridement. Eighteen patients were cured, 8 failed to respond to treatment, and one was lost to follow-up. The duration of clarithromycin (147 vs. 28; p = 0.0297), and rifampicin (201 vs. 91; p = 0.0266) treatment in the cured patients was longer than that in the others. Surgical debridement was performed in 10 out of the 18 cured patients, and in 1 of another group (p = 0.0417). All the 30 isolates were susceptible to clarithromycin, amikacin, and linezolid; 29 (96.7%) were susceptible to ethambutol; 28 (93.3%) were susceptible to sulfamethoxazole; and 26 (86.7%) were susceptible to rifampicin. However, only 1 (3.3%) isolate was susceptible to doxycycline.
Discussion: Early diagnosis of the infection and appropriate antimicrobial therapy with surgical debridement are the mainstays of successful treatment. Clarithromycin and rifampin are supposed to be more effective agents.