A University of Leicester researcher has discovered how a protein in the blood linked to defence against meningitis plays a more vital role than previously understood in the body’s immune defence system. The published research has helped to advance medical understanding of how the body defends against disease and heals itself. The study also reveals that the same protein, properdin – discovered half a century ago - can also harm internal organs under certain circumstances. Lack of the protein in the human body has previously been linked to susceptibility to meningitis. But the new findings by Cordula Stover of the Department of Infection, Immunity and Inflammation at the University of Leicester assign hitherto unappreciated importance to this protein of the immune defence. Dr Stover, a Lecturer in Immunology, said:
I have a broad interest in immune mechanisms of health and disease, though recently, I have focused on a particular component of the first line immune defence, a protein called properdin. Properdin deficiency in families, though rare, predisposes people to develop meningococcal meningitis, usually with poor outcome of the infection. I hypothesised that the importance of properdin extends beyond this particular infectious disease, and that indeed it is an important player in health generally, and that its importance becomes apparent in conditions involving both acute and chronic states of inflammation.
Now Dr Stover’s paper published in the Journal of Immunology demonstrates that properdin plays a significant role in the survival of conditions relating to surgical perforation of the gut and activation of the immune system by wall components of bacteria. In conditions relating to multi-organ dysfunction, a complication which can occur in response to severe sepsis, properdin however aggravates organ damage.
So far, the system properdin is a part of - the so-called complement system - is classified as a first line, innate, acutely effective immune activation mechanism. This work shows that the activity of properdin extends beyond the acute phase and, importantly, that properdin is stepping onto the stage as an important player in different inflammatory conditions. As the worldwide burden of chronic inflammatory disease increases, it is of practical relevance to understand the contribution of this immune protein.
Bacteriophages are among the smallest but most abundant organisms on earth. For most phages, the tail mediates the anchoring of the phage to generally abundant bacterial outer membrane proteins that serve as specific receptors for their substrates. For example, the receptor for the temperate phage λ is the Escherichia coli maltoporin receptor LamB, which functions in amylomaltose uptake. The establishment of a stable phage–host interaction relays signals that allow injection of DNA from the phage capsid through the tail and into the host, leaving the empty capsid (head) attached to the cell surface. Following phage λ DNA injection, a decision between the lytic or lysogenic pathways of bacteriophage λ is made. The poles (ends) of bacterial calls have specialized functions related to the mobilization of DNA and certain proteins. To monitor the infection of Escherichia coli cells by light microscopy, scientists developed procedures for the tagging of mature bacteriophages with quantum dots:
Surprisingly, most of the infecting phages were found attached to the bacterial poles. This was true for a number of temperate and virulent phages of E. coli that use widely different receptors and for phages infecting Yersinia pseudotuberculosis and Vibrio cholerae. The infecting phages colocalized with the polar protein marker IcsA–GFP. ManY, an E. coli protein that is required for phage λ DNA injection, was found to localize to the bacterial poles as well. Furthermore, labelling of λ DNA during infection revealed that it is injected and replicated at the polar region of infection. The evolutionary benefits that lead to this remarkable preference for polar infections may be related to λ’s developmental decision as well as to the function of poles in the ability of bacterial cells to communicate with their environment and in gene regulation.
By labelling different phages with quantum dots and following adsorption using a fluorescence microscope the researchers were able to investigate the initial steps of binding (adsorption) and phage DNA injection. The surprising results showed that at low multiplicities of infection, phages preferentially adsorb, inject and replicate their DNA at the bacterial poles. This spatial preference was independent of host proteins, ManY and Pel, required for phage λ DNA injection. The significance of the pole, the binding of the phage to the pole and its implications in lytic-lysogenic decision are discussed in the paper.
The sociobiology of bacteria, largely unappreciated and ignored by the microbiology research community two decades ago is now a major research area, catalyzed to a significant degree by studies of communication and cooperative behavior among the myxobacteria and in quorum sensing (QS) and biofilm formation by pseudomonads and other microbes. Recently, the topic of multicellular cooperative behaviors among bacteria has been increasingly considered in the context of evolutionary biology. This essay discusses the significance of two recent studies of the phenomenon of “cheating” mutants and their exploitation of cooperating microbial populations of Pseudomonas aeruginosa.
Magnetic or “magnetotactic” bacteria were first discovered in the 1960s, and naturally organize themselves in the direction of Earth’s magnetic field, as shown in this video:
Inside these bacteria there is a row of iron-containing crystals aligned with the long axis of the cell, giving them the equivalent of an internal magnetic compass needle (Molecular mechanisms of magnetosome formation. Ann Rev Biochem 2007 76: 351-66). Such bacteria can sense and align themselves relative to the earth’s magnetic field. Magnetotactic bacteria are major constituents of many natural microbial communities, especially in aquatic habitats. There is a broad range of shapes and groups of magnetic bacteria. However, cultivation of these organisms in the laboratory is often difficult and only few strains of magnetotactic bacteria have been isolated in pure culture, a tiny minority of the vast diversity of naturally occurring populations from largely unexplored natural habitats such as the marine environment.
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So why would bacteria want to be magnetic? Leaving aside the possibility that they are magnetic by accident, e.g. as a consequence of some metabolic byproduct, the truth is that we really don’t know the reason. However, the most likely explanation lies not in north-south alignment, but in up and down. The magnetotactic bacteria we know about require low but very precise levels of oxygen to survive, and must live in sediments where the oxygen concentration is just right for their needs. Over much of the globe, the Earth’s magnetic field actually points down towards the centre of the planet, so by following these lines of magnetic flux, they are able to ensure that they bury themselves in the sediment, which is exactly where they want to be. Thus the majority of magnetotactic in the Northern Hemisphere are north seeking, and those in the Southern Hemisphere are south seeking.
An antibody present in people with good oral health could become the first tool for dentists to assess a patient’s probable response to periodontal (gum) disease treatments. The antibody is to a protein called HtpG, made by the bacterium Porphyromonas gingivalis, an important pathogen in periodontal disease. The antibody also has potential as a vaccine candidate. Researchers discovered that the HtpG antibodies were present in much lower amounts in people with periodontal disease and in much higher concentrations in those with healthier teeth and gums. Typically, antibodies are elevated in people with disease, because they help fight the disease.
What has been seen in periodontal disease over the last 30-40 years is that patients with periodontal disease have higher levels of antibodies to the bacteria associated with periodontal disease, but these antibodies are not usually protective. The healthy patient makes high levels of the antibodies but to the right part of the organism. Not only were the HtpG antibodies present in higher amounts in people with healthier gums, those patients with the antibodies responded better to periodontal treatment.
The United States spends $8-$12 billion a year caring for people with serious periodontal disease. From a public health standpoint, it is important to identify those people who not only need therapy but will actually respond to a specific type of therapy. In the long run, this could lead to early interventional therapy to prevent periodontal disease from advancing, or even starting. The other part of the question is why people with periodontal disease do not make a good immune response to HtpG, and this could connect back to current thinking that oral health influences general health.
Both friendly and destructive bacteria live in our mouths, eyes, skin and elsewhere. Over millions of years, the body has come to an accommodation with those creatures, generally striking a balance ensuring survival. This balance has been severely offset in recent years, due to a “cleanliness” obsession that arose when it became clear that some germs were responsible for diseases. This idea was effectively demonstrated by UK researcher David Strachan, whose research led to what is now called the “hygiene hypothesis” - respiratory illnesses result from lack of cross-microbe activity to build immunities. In short, rich, small families were more prone to allergies than large, poorer ones. As Sachs points out, humans in our society overreacted to the new knowledge about disease-causing germs and sought to eliminate them all. The imbalance has led to many tragic situations, and initiated a guarantee that more, perhaps worse, situations are in the offing. What are we to do about it?
Jessica Sachs guides us through the findings of scores of scientists’ work that has revised the approach we were taught about “germs” in our childhood. Eating mud, something many of us were at least verbally chastised for, turns out to be a good thing, even a necessity. From birth, the introduction of certain microbes initiate processes the body needs to keep going. For most people today, it’s well known that microbes in our tummies are part of the process of digestion. Escherichia coli is known to be a true friend - in controlled numbers and certain strains. What’s less known is how many other bacteria the body relies on to get certain jobs done. One of those jobs is keeping the immune system properly tuned. A lazy immune system is unresponsive or unable to react to invasion. An overly ambitious one can turn on its own body and destroy it.
Publisher Hill & Wang, Oct 2007, ISBN-10: 0809050633
We spend most of our lives in indoor environments and are exposed to microbes present in these environments. Hence, knowledge about this exposure is important for understanding how it impacts on human health. However, the bacterial flora in indoor environments has been only fragmentarily explored and mostly using culture methods. The application of molecular methods previously utilised in other environments has resulted in a substantial increase in our awareness of microbial diversity. The composition and dynamics of indoor dust bacterial flora were investigated in two buildings over a period of one year. Four samples were taken in each building, corresponding to the four seasons, and 16S rDNA libraries were constructed.
All libraries were dominated by Gram-positive sequences, with the most abundant phylum being Firmicutes. Four OTUs having high similarity to Corynebacterium, Propionibacterium, Streptococcus and Staphylococcus sequences were present in all samples. The most abundant of the Gram-negative OTUs were members of the family Sphingomonadaceae, followed by Oxalobacteraceae, Comamonadaceae, Neisseriaceae and Rhizobiaceae. The relative abundance of alpha- and betaproteobacteria increased slightly towards summer at the expense of firmicutes. The proportion of firmicutes and gammaproteobacteria of the total diversity was highest in winter and that of actinobacteria, alpha- and betaproteobacteria in spring or summer, whereas the diversity of bacteroidetes peaked in fall. A statistical comparison of the libraries revealed that the bacterial flora of the two buildings differed during all seasons except spring, but differences between seasons within one building were not that clear, indicating that differences between the buildings were greater than the differences between seasons. This work demonstrates that the bacterial flora of indoor dust is complex and dominated by Gram-positive species. The dominant phylotypes most probably originated from users of the building. Seasonal variation was observed as proportional changes of the phyla and at the species level. The microflora of the two buildings investigated differed statistically and differences between the buildings were more pronounced than differences between seasons.
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Every year, nearly nine million people develop tuberculosis and about two million people die from the disease. Diagnostic tests for tuberculosis include chest X-rays, the tuberculin skin test, and sputum analysis. For the last of these tests, a sample of sputum (mucus and other matter brought up from the lungs by coughing) is collected and examined under the microscope for M. tuberculosis using special stains and also by trying to grow bacteria from the sample. Tuberculosis can be cured by taking several different antibiotics for several months. It is very important that this treatment is completed to ensure that all the tuberculosis bacteria in the body are killed and to prevent the emergence of drug-resistant bacteria. Very little is known about the efficiency with which M. tuberculosis spreads from one person to another.
The researchers collected sputum samples from patients with tuberculosis in the UK and in The Gambia before they had received any treatment. They looked for the presence of acid-fast bacilli containing “lipid bodies”, small structures within the cells containing a fat called triacylglycerol. M. tuberculosis accumulates triacylglycerol when it is exposed to stresses present during infection (for example, reduced oxygen, hypoxia) and it was thought that that the presence of this fat may help the bacteria survive during transmission and establish a new infection. M. tuberculosis grown in the laboratory under hypoxic conditions, which induces the bacteria to enter an antibiotic-tolerant condition called a “nonreplicating persistent” (NRP) state, accumulated lipid bodies. The researchers compared the pattern of mRNAs made by actively growing cultures of M. tuberculosis, M. tuberculosis maintained in the NRP state, and by acid-fast bacilli from sputum samples. The transcriptome of the sputum sample revealed production of many proteins made in the NRP state. Finally, they showed that the time needed to grow M. tuberculosis from sputum samples increased as the proportion of lipid body–positive acid-fast bacilli in the sputum increased.
The characteristics of this population of bacteria might help them survive the adverse conditions that M. tuberculosis encounters during transmission between people and might partly explain why complete clearance of M. tuberculosis requires extended treatment with antibiotics. To establish the clinical significance of these findings, future studies will need to examine whether antibiotic treatment affects the frequency of lipid–positive bacteria in sputum and whether there is any relationship between this measurement and infectiousness, or clinical response to treatment. Professor Mike Barer says:
These surprising findings have opened the door for us to develop new ways to stop TB from spreading and to treat it more effectively. We hope that our new ability to monitor these sleepy and resistant bacteria in sputum will enable us to treat the disease more quickly.
The environmental persistence of Mycobacterium tuberculosis is subject to speculation. However, the reality that infected postmortem tissues can be a danger to pathologists and embalmers has worrisome implications. A few experimental studies have demonstrated the organism’s ability to withstand exposure to embalming fluid and formalin. Recently, a failure was reported in an attempt to resuscitate an original isolate of Robert Koch to determine the lifetime of the tubercle bacillus. This study considers a historical approach to determine persistence under favorable environmental conditions and asks whether acid-fast forms observed in tissues of 300-year-old Hungarian mummies can be resuscitated. Finding organisms before the advent of antibiotics and pasteurization may yield valuable genetic information. Using various media modifications, as well as guinea pig inoculation, an attempt was made to culture these tissues for M. tuberculosis. In addition, a resuscitation-promoting factor, known to increase colony counts in high G+C bacteria, was applied to the cultures. Although an occasional PCR-positive sample was detected, no colonies of M. tuberculosis were obtained. Our results may indicate that the life span of the tubercle bacillus is less than a few hundred years, even though in the short run it can survive harsh chemical treatment.
In this article in Microbiology Today (February 200 , Dave Spratt gives us an overview of the life in our mouths, which is more complex than we imagine:
The oral cavity forms the top section of the gastrointestinal tract and provides a large number of diverse surfaces on which a wide variety of complex biofilms is able to form. These surfaces include soft shedding tissues of the buccal mucosa, papillae and crypts of the tongue and hard non-shedding surfaces of the teeth. Dental plaque is the term commonly used for the biofilm formed on teeth; however, the term plaque has now been extended to encompass biofilms on all the oral surfaces. These biofilms consist of a complex microbial community embedded in a matrix of polymers of bacterial and salivary origin…
Both friendly and destructive bacteria live in our mouths, eyes, skin and elsewhere. Over millions of years, the body has come to an accommodation with those creatures, generally striking a balance ensuring survival. This balance has been severely offset in recent years, due to a “cleanliness” obsession that arose when it became clear that some germs were responsible for diseases. This idea was effectively demonstrated by UK researcher David Strachan, whose research led to what is now called the “hygiene hypothesis” - respiratory illnesses result from lack of cross-microbe activity to build immunities. In short, rich, small families were more prone to allergies than large, poorer ones. As Sachs points out, humans in our society overreacted to the new knowledge about disease-causing germs and sought to eliminate them all. The imbalance has led to many tragic situations, and initiated a guarantee that more, perhaps worse, situations are in the offing. What are we to do about it?
