Posts Tagged ‘Bacteria’

Exploiting bacteriophages for human health

Thursday, March 27th, 2014

Exploiting bacteriophages for human health Whenever I write about phage therapy – using bacteriophages to treat bacterial infections – readers get overly enthusiastic about injecting patients with phages to produce a miracle cure. Look at it this way – that hasn’t worked for the last 100 years and it’s not likely to suddenly start working now. This short review is worth reading because it takes a much more thoughtful and holistic approach to the idea of phage therapy than the simple minded “phage as wonder cure” idea.

Exploiting gut bacteriophages for human health. Trends Microbiol. 20 Mar 2014 pii: S0966-842X(14)00045-6. doi: 10.1016/j.tim.2014.02.010
The human gut contains approximately 1015 bacteriophages (the ‘phageome’), probably the richest concentration of biological entities on earth. Mining and exploiting these potential ‘agents of change’ is an attractive prospect. For many years, phages have been used to treat bacterial infections in humans and more recently have been approved to reduce pathogens in the food chain. Phages have also been studied as drug or vaccine delivery vectors to help treat and prevent diseases such as cancer and chronic neurodegenerative conditions. Individual phageomes vary depending on age and health, thus providing a useful biomarker of human health as well as suggesting potential interventions targeted at the gut microbiota.

Microbiology Today – microbial superheroes

Thursday, February 27th, 2014

The latest issue of Microbiology Today – microbial superheroes is available for download from http://www.sgm.ac.uk/en/publications/microbiology-today/current-issue.cfm

Microbiology Today - microbial superheroes

In this issue:

The shape-shifting superhero: Dictyostelium discoideum
This social amoeba has superhero, shape-shifting qualities, and is able to switch between a unicellular and a multicellular existence.

Diatoms: glass-dwelling dynamos
Superheroes have a reputation for being larger than life, but it is the unseen micro- organisms such as diatoms that can have a substantial impact on our lives.

The immortal, halophilic superhero: Halobacterium salinarum – a long-lived poly-extremophile
Halobacterium salinarum is an extremophile superhero on at least three counts: how are its extreme halophily, radiation resistance and longevity interconnected?

Heroic exertion of radiation-resistant extremophiles
An overview of ‘super’ radiation-resistant extremophiles and their potential uses in biotechnology and medicine.

Herpes simplex virus – master of disguise and invisibility
Invisibility would probably be high on anyone’s wish list of superpowers. But HSV has got there first.

 

Quorum Sensing Genes Discovered in a Bacteriophage

Thursday, January 30th, 2014

phiCDHM1 Some groundbreaking new research from my Leicester colleagues that’s too good to resist blogging about:

The incorporation of host DNA into phage genomes occurs across diverse bacteria, and acquisition of bacterial genes facilitates phage evolution. Although small, phage genomes have a high proportion of coding sequence relative to their size. The extent by which virus genomes can increase is constrained physically by the dimensions of their virion particles in which their DNA is packaged, by fitness costs associated with phage production, and by their packaging strategy. Although genetic material can be acquired via transduction and during DNA packaging, phage genomes are considered to be highly reduced and non-beneficial genes are lost through selective evolution. Therefore, discoveries of bacterial gene homologs in addition to the “core” phage genome are interesting, as is the diverse nature of these host associated genes.

Clostridium difficile is a major pathogen in healthcare settings, causing antibiotic associated diarrheal disease which can be fatal. Novel strains continue to emerge in clinical settings, and potential reservoirs of the bacterium include asymptomatic humans, wild and domesticated animals, and the natural environment. C. difficile pathogenicity can also be altered by the differential expression of their virulence genes, controlled via quorum sensing (QS) which is a form of bacterial communication. Through quorum sensing, cells communicate to the surrounding population via the release and detection of signalling molecules which elicit a physiological response. This paper describes the discivery of homologs of QS genes in a phage of C. difficile.

While the action and consequences of these phage QS genes is unclear, their presence and transcription during infection in a lysogenic and lytic background presents an exciting method by which phages can manipulate their hosts.

 

What Does the Talking?: Quorum Sensing Signalling Genes Discovered in a Bacteriophage Genome. (2014) PLoS ONE 9(1): e85131. doi:10.1371/journal.pone.0085131
The transfer of novel genetic material into the genomes of bacterial viruses (phages) has been widely documented in several host-phage systems. Bacterial genes are incorporated into the phage genome and, if retained, subsequently evolve within them. The expression of these phage genes can subvert or bolster bacterial processes, including altering bacterial pathogenicity. The phage phiCDHM1 infects Clostridium difficile, a pathogenic bacterium that causes nosocomial infections and is associated with antibiotic treatment. Genome sequencing and annotation of phiCDHM1 shows that despite being closely related to other C. difficile myoviruses, it has several genes that have not been previously reported in any phage genomes. Notably, these include three homologs of bacterial genes from the accessory gene regulator (agr) quorum sensing (QS) system. These are; a pre-peptide (AgrD) of an autoinducing peptide (AIP), an enzyme which processes the pre-peptide (AgrB) and a histidine kinase (AgrC) that detects the AIP to activate a response regulator. Phylogenetic analysis of the phage and C. difficile agr genes revealed that there are three types of agr loci in this species. We propose that the phage genes belonging to a third type, agr3, and have been horizontally transferred from the host. AgrB and AgrC are transcribed during the infection of two different strains. In addition, the phage agrC appears not to be confined to the phiCDHM1 genome as it was detected in genetically distinct C. difficile strains. The discovery of QS gene homologs in a phage genome presents a novel way in which phages could influence their bacterial hosts, or neighbouring bacterial populations. This is the first time that these QS genes have been reported in a phage genome and their distribution both in C. difficile and phage genomes suggests that the agr3 locus undergoes horizontal gene transfer within this species.

The Role of Archaea in Human Disease

Thursday, January 23rd, 2014

Archaea The Archaea, the so-called Third Domain of life, are thought of in an environmental context, influencing natural environments and ecosystems including extreme environments such as salt lakes and soda lakes. But what if some species were capable of capable of causing human disease? Currently, there is no substantial evidence supporting the pathogenic properties of Archaea. This free review article considers why.

 

Role of archaea in human disease. (2013) Front Cell Infect Microbiol. 3:42. doi: 10.3389/fcimb.2013.00042

 

Communication between bacteria and their hosts

Tuesday, January 14th, 2014

Bacteria Although bacterial growth and virulence are influenced by local environmental parameters such as temperature, pH, and nutrient availability, the influence of host signals on bacterial behaviour has only recently become apparent. Microbial endocrinology is a newly recognised research area that has as its foundation the idea that through their long coexistence with animals and plants, microorganisms have evolved systems for sensing host-associated chemicals such as hormones. These hormone sensors enable the microbe to recognise that they are within the locality of a suitable host and, for commensals, that it is the appropriate time to initiate expression of genes involved in host colonisation or in the case of pathogens, genes for virulence determinants. This review by my Leicester colleague Primrose Freestone explores the discusses the bidirectional communication taking place between microorganisms and their hosts via chemical signals.

Freestone, P. (2013) Communication between bacteria and their hosts. Scientifica, 2013. http://dx.doi.org/10.1155/2013/361073
It is clear that a dialogue is occurring between microbes and their hosts and that chemical signals are the language of this interkingdom communication. Microbial endocrinology shows that, through their long coexistence with animals and plants, microorganisms have evolved sensors for detecting eukaryotic hormones, which the microbe uses to determine that they are within proximity of a suitable host and to optimally time the expression of genes needed for host colonisation. It has also been shown that some prokaryotic chemical communication signals are recognized by eukaryotes. Deciphering what is being said during the cross-talk between microbe and host is therefore important, as it could lead to new strategies for preventing or treating bacterial infections.

Close Encounters of the Third Domain

Tuesday, January 7th, 2014

Bacterial origins If you’re new to microbiology (or even if you’re not), this short review is an easily accessible introduction to the the three (cellular) domains of life – Eukarya, Bacteria, and Archaea.

Close Encounters of the Third Domain: The Emerging Genomic View of Archaeal Diversity and Evolution. Archaea, 2013. http://dx.doi.org/10.1155/2013/202358
The Archaea represent the so-called Third Domain of life, which has evolved in parallel with the Bacteria and which is implicated to have played a pivotal role in the emergence of the eukaryotic domain of life. Recent progress in genomic sequencing technologies and cultivation-independent methods has started to unearth a plethora of data of novel, uncultivated archaeal lineages. Here, we review how the availability of such genomic data has revealed several important insights into the diversity, ecological relevance, metabolic capacity, and the origin and evolution of the archaeal domain of life.

 

What is it about amyloids?

Tuesday, December 10th, 2013

Curli Amyloids are insoluble fibrous protein aggregates with a beta sheet structure. They have had a lot of bad publicity because they are associated with diseases such as Alzheimer’s, Huntington’s, and the spongiform encephalopathies associated with prions. In these conditions, the deposits of amyloid protein within nerve cells are toxic and lead to the death of cells and consequent neurological symptoms. But recently, we have slowly become aware that amyloids are not necessarily “evil” and that “functional” amyloids contribute to normal cellular biology, being used as structural elements by lower organisms and involved in the production of proteins such as melanin.

So what is it about amyloids – why are they so widespread in living organisms? The amyloid fold which produces the characteristic beta sheet structure of all amyloids is a pre-programmed event, so amyloid polymers can self-assemble without any exogenous energy, inside or outside the cell from which they originate. Once made, amyloid polymers are resistant to harsh conditions that would denature most proteins – a pretty useful characteristic. A new article in PLOS Pathogens looks at the various roles of bacterial amyloids in host, polymicrobial, and environmental interactions and makes some interesting suggestions (Disease to Dirt: The Biology of Microbial Amyloids. (2013) PLoS Pathog 9(11): e1003740. doi:10.1371/journal.ppat.1003740).

Amyloid fibres are common as part of the extracellular matrix that holds biofilms together. It is easy to see how useful amyloid is in this environment. The fibres are produced extracelluarly and reinforce the complex protein and polysaccharide matrix of the biofil that protects the communities of cells it contains. Escherichia coli, Salmonella enterica serovar Typhimurium, Bacillus subtilis, Staphylococcus aureus, Mycobacterium tuberculosis, and many others, all produce extracellular amyloid fibers, as do between 5–40% of species isolated from natural biofilms found in seawater, sludge, and drinking water. Amyloids are very common then, but they do much more than acting as reinforcing rods in the biofilm matrix.

Curli are fibres composed of amyloid found in the complex extracellular matrix produced by many Enterobacteriaceae such as E. coli and Salmonella (Curli biogenesis and function. (2006) Annu Rev Microbiol. 60: 131-47). Curli are involved in adhesion to surfaces, cell aggregation, biofilm formation and mediate host cell adhesion and invasion, and they are potent inducers of the mammalian inflammatory response and plant hypersensitive immune response. This is where it gets interesting because in this context amyloid has moved from being mere structural reinforcement to what is now known as “functional amyloid”. In come cases curli act as adhesins, and in a few cases (such as Klebsiella pneumoniae), as toxins which can trigger apoptosis in human cells.

The reason amyloid has had such as bad press is because the tangled plaques of amyloid fibrils found in conditions such as Alzheimer’s diseases are clearly examples of amyloid formation at the wrong time, in the wrong place or with the wrong constituents. Mature amyloid fibrils do not appear to be inherently toxic if handled appropriately by the cell and essential components of many aspects of cell biology. Finding out more about the normal as opposed to the abnormal biology of amyloid will have great benefits in understanding bacterial growth and pathogenesis. This knowledge could lead to potential therapies or probiotics to designed beneficially exploit amyloid formation in the host and environment or to counteract bacterial cell invasion mechanisms.

 

The battle against TB

Tuesday, December 3rd, 2013

The Guardian I have written a lot on MicrobiologyBytes about tuberculosis (TB) as a remerging disease, but the global TB situation is still poor, so it’s always worth bringing this issue to people’s attention again. Writing in The Guardian, Nick Herbert points out the painfully slow progress which has been made (The fight against TB is not over):

The rate of new cases of TB has been falling worldwide for about a decade, enough to hit a UN millennium development goal target, and deaths will have nearly halved since 1990. But a decline of 2% a year in the estimated incidence rate suggests that the disease is being beaten at a shamefully slower rate than when the west tackled it a century ago. On current progress it will take at least another 100 years. The latest World Health Organisation report, published last month, warned that 3 million people a year who develop TB are being missed by health programmes. Most worryingly, less than a quarter of drug-resistant cases are being detected and less than half of those that are detected are successfully treated.

So hats off to Mr Herbert for highlighting this important issue. But this is The Guardian, and the byline to this story includes the phrase “western leaders need to act now“. Mr Herbert points out that:

London has the highest rates of TB of any city in western Europe. The borough of Newham has rates equivalent to Nigeria.

All of which is true. Commenters on The Guardian article weren’t slow to mention that Nick Herbert is a serving Tory MP, who was previously director of public affairs at the British Field Sports Society for six years. While the editorial process at The Guardian has ensured that the facts in Mr Herbert’s article are correct, it’s hard to disentangle this piece from the Tory agenda on limiting immigration and the aftermath of the failed badger cull.

So yes, we need to do more about TB, as some of us have been pointing out for years. But we also need to be critical and questioning about where we acquire information and how we react to it. Politicians and science generally don’t mix. On the whole, that’s a good thing – there’s already too much politics in science.

 

Farmer Fungus

Tuesday, November 26th, 2013

Morchella crassipes Humans think they’re so smart, giving themselves credit for inventing stuff like the the wheel, fire, and agriculture. Well think again, because we’re not the first to invent farming. Cultivation of crops for nourishment has evolved a few times among eukaryotes. The best known examples include ants, termites, beetles, and, around 10,000 years ago, humans. It turns out that the soil fungus Morchella crassipes acts as a bacterial farmer, involving habitual planting, cultivation and harvesting of bacteria.

It’s fairly obvious what the fungus gets out of this arrangement – it’s in it for all the lovely reduced carbon those tasty bacteria provide. But what about the bacteria – do they get some benefit from the arrangement? It seems that they might. Soil is not the easiest medium for cells to disperse in, and by using the fungal hyphae as a sort of motorway network, this would seem to be more of a mutualistic arrangement, albeit one in which some of the cells wind up as lunch for the farmer.

Bacterial farming by the fungus Morchella crassipes. (2013) Proceedings of the Royal Society B: Biological Sciences, 280(1773), 20132242.