MicrobiologyBytes

Researchers examined the responses of various microorganisms (viruses, bacterial cells, bacterial and fungal spores, and lichens) to selected factors of space (microgravity, galactic cosmic radiation, solar UV radiation, and space vacuum) in space and laboratory simulation experiments. In general, microorganisms tend to thrive in the space flight environment in terms of enhanced growth parameters and a demonstrated ability to proliferate in the presence of normally inhibitory levels of antibiotics. The mechanisms responsible for the observed biological responses, however, are not yet fully understood. A hypothesized interaction of microgravity with radiation-induced DNA repair processes was experimentally refuted.

The survival of microorganisms in outer space was investigated to tackle questions on the upper boundary of the biosphere and on the likelihood of interplanetary transport of microorganisms. It was found that extraterrestrial solar UV radiation was the most deleterious factor of space. Among all organisms tested, only lichens (Rhizocarpon geographicum and Xanthoria elegans) maintained full viability after 2 weeks in outer space, whereas all other test systems were inactivated by orders of magnitude. Using optical filters and spores of Bacillus subtilis as a biological UV dosimeter, it was found that the current ozone layer reduces the biological effectiveness of solar UV by 3 orders of magnitude. If shielded against solar UV, spores of B. subtilis were capable of surviving in space for up to 6 years, especially if embedded in clay or meteorite powder (artificial meteorites). The data support the likelihood of interplanetary transfer of microorganisms within meteorites, the so-called lithopanspermia hypothesis.

Space microbiology. (2010) Microbiol Mol Biol Rev. 74(1): 121-56

Related:

• They Came From Space – or did they?
• Bugs in space
• Is microbial life on Mars possible?

Indoor environments, where the average person in an industrial nation spends ~90% of his or her life, represent the most important interface between humans and microbes. Examples of well-known fungi include a few human pathogens, allergens, agents of structural rot and food spoilers. Indoor fungi’s prominent role in successful litigation around the world contributes to rising costs for various industries and insurance companies. Increasingly strict standards for indoor sanitation have resulted in regulatory agencies and private industries seeking to quantify building health. Mould surveys that target the relatively few visibly apparent fungal species or those readily cultivable on artificial media are now standard, and a U.S. Environmental Protection Agency-developed set of real-time PCR probes facilitates their quantification. However, the recent rise in fungal infections caused by species formerly considered benign but now seen as causing disease in immunosuppressed humans, and a vastly increased resolution of indoor fungal composition afforded by culture-independent sampling methods, force us to reconsider what constitutes a normal indoor environment and the factors that shape it. Recent efforts to describe the processes shaping indoor and urban fungal composition show temporal effects and modest correlations with human activity. The existence of global-scale patterns in fungal composition, however, is unexamined, despite evidence of biogeographical patterning in other microbial systems.

As with larger organisms, bacterial and archaeal composition is determined by both the contemporary environment and historical processes such as dispersal. The relative importance of these factors and the particular environmental variables involved depend on the taxa and habitat sampled. For indoor fungi whose association with highly mobile humans presents opportunities for global dispersal, it was presumed that most taxa would be relatively cosmopolitan on a global scale, and that the local indoor environment (as determined by building function, construction material, or circulation system) would play a relatively large role in shaping composition. As a result of the combination of presumably high dispersal rates between indoor habitats and the highly selective indoor environment, little influence of the outdoor environment was expected on fungal composition. But are these assumptions true?

Indoor fungal composition is geographically patterned and more diverse in temperate zones than in the tropics. PNAS USA June 28 2010 doi: 10.1073/pnas.100045410
Fungi are ubiquitous components of indoor human environments, where most contact between humans and microbes occurs. The majority of these organisms apparently play a neutral role, but some are detrimental to human lifestyles and health. Recent studies that used culture-independent sampling methods demonstrated a high diversity of indoor fungi distinct from that of outdoor environments. Others have shown temporal fluctuations of fungal assemblages in human environments and modest correlations with human activity, but global-scale patterns have not been examined, despite the manifest significance of biogeography in other microbial systems. Here we present a global survey of fungi from indoor environments using both taxonomic and phylogeny-informative molecular markers to determine whether global or local indoor factors determine indoor fungal composition. Contrary to common ecological patterns, we show that fungal diversity is significantly higher in temperate zones than in the tropics, with distance from the equator being the best predictor of phylogenetic community similarity. Fungal composition is significantly auto-correlated at the national and hemispheric spatial scales. Remarkably, building function has no significant effect on indoor fungal composition, despite stark contrasts between architecture and materials of some buildings in close proximity. Distribution of individual taxa is significantly range- and latitude-limited compared with a null model of randomized distribution. Our results suggest that factors driving fungal composition are primarily global rather than mediated by building design or function.

Related:

• Is Everything Everywhere?
• New Strain of Virulent Airborne Fungus Looks Set to Spread
• Is air conditioning a health hazard?

Candida infections are the fourth most common cause of nosocomial blood stream infections and are associated with a significant mortality. Delays in antifungal therapy have been associated with increased hospital costs of over US$6,000 per patient and overall mortality. The role of HMG CoA reductase inhibitors (statins) in improving outcomes bacteremic sepsis is currently being debated with recent papers showing significantly improved survival in patients with systemic inflammatory response syndrome in the intensive care unit, in patients with chronic kidney renal disease and patients with community acquired pneumonia and influenza. One explanation of this effect is that statins in animal models have shown to reduce inflammatory markers, in particular the release of cytokines and cytotoxic effects of neutrophils. The reduction in inflammatory cytokines has also been demonstrated in patients in a prospective randomized study comparing simvastatin to placebo where there was a significant reduction in tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in the statin group. Yeasts use the same HMG CoA reductase as humans, however their end-product is ergosterol rather than cholesterol. In vitro studies have demonstrated that simvastatin greatly inhibits the growth of Candida species. This review suggests there is a clinical benefit of statin therapy throughout antifungal therapy in intensive care unit patients with confirmed candidemia.

Statins in Candidemia: clinical outcomes from a matched cohort study. 2010 BMC Infectious Diseases 10: 152 doi:10.1186/1471-2334-10-15210
HMG CoA reductase inhibitors (statins) in patients with bacteremic sepsis have shown significant survival benefits in several studies. There is no data on the effect of statins in candidemic patients, however in-vitro models suggest that statins interfere with ergesterol formation in the wall of yeasts.
This retrospective matched- cohort study from 1/2003 to 12/2006 evaluated the effects of statins on patients with candidemia within intensive care units. Statin-users had candidemia as a cause of their systemic inflammatory response and were on statins throughout their antifungal therapy, while non-statin-users were matched based on age +/- 5 years and co-morbid factors. Primary analysis was 30-day survival or discharge using bivariable comparisons. Multivariable comparisons were completed using conditional logistic regression. All variables with a p-value less than 0.10 in the bivariable comparisons were considered for inclusion in the conditional logistic model.
There were 15 statin-users and 30 non-statin users that met inclusion criteria, all with similar demographics and co-morbid conditions except the statin-users had significantly more coronary artery disease (P<0.01), peripheral vascular disease (P=0.03) and lower median APCAHE II scores (p=0.03). There were no differences in duration of candidemia , antifungal therapy or Candida species between the groups. Statins were associated with lower mortality on bivariable and multivariable analyses compared to controls; although, in the latter the protective effect lacked statistical signficance.
In our small, single-center matched cohort study, statins appear may provide a survival benefit in candidemia, however further studies are warranted to validate and further explore this association.

Related:

• All About Fungi: Part 1
• All About Fungi: Infection
• How human pathogenic fungi sense and adapt to pH

Bats, which are ‘keystone species’ in many ecosystems, play notable roles in plant pollination, forest regeneration and control of insect populations. Bats are important to human health as they are reservoirs or carriers for rabies and other viruses, parasites, and pathogenic fungi. Hibernation is believed to be an important adaptation in bats that may contribute to their exceptional longevity. The common little brown bat (Myotis lucifugus) hibernates, along with the endangered Indiana bat (Myotis sodalis), in many hibernacula in the Northeastern United States, including caves and mines in upstate New York. Hibernating bats can suffer significant mortality due to adverse environmental conditions such as freezing or flooding, as well as human activities including visitation and pesticide applications. No mass mortality was reported until recently from bat sites that had been surveyed for almost three decades by the New York State Department of Environmental Conservation. Recently, however little brown bats have been found to be dying in large numbers at many hibernation sites in upstate New York. This problem has spread to other States in the Northeastern USA.

Morphological and Molecular Characterizations of Psychrophilic Fungus Geomyces destructans from New York Bats with White Nose Syndrome (WNS). PLoS ONE 5(5): e10783. doi:10.1371/journal.pone.0010783
Massive die-offs of little brown bats (Myotis lucifugus) have been occurring since 2006 in hibernation sites around Albany, New York, and this problem has spread to other States in the Northeastern United States. White cottony fungal growth is seen on the snouts of affected animals, a prominent sign of White Nose Syndrome (WNS). A previous report described the involvement of the fungus Geomyces destructans in WNS, but an identical fungus was recently isolated in France from a bat that was evidently healthy. The fungus has been recovered sparsely despite plentiful availability of afflicted animals.
We have investigated 100 bat and environmental samples from eight affected sites in 2008. Our findings provide strong evidence for an etiologic role of G. destructans in bat WNS. (i) Direct smears from bat snouts, Periodic Acid Schiff-stained tissue sections from infected tissues, and scanning electron micrographs of bat tissues all showed fungal structures similar to those of G. destructans. (ii) G. destructans DNA was directly amplified from infected bat tissues, (iii) Isolations of G. destructans in cultures from infected bat tissues showed 100% DNA match with the fungus present in positive tissue samples. (iv) RAPD patterns for all G. destructans cultures isolated from two sites were indistinguishable. (v) The fungal isolates showed psychrophilic growth. (vi) We identified in vitro proteolytic activities suggestive of known fungal pathogenic traits in G. destructans.
Further studies are needed to understand whether G. destructans WNS is a symptom or a trigger for bat mass mortality. The availability of well-characterized G. destructans strains should promote an understanding of bat–fungus relationships, and should aid in the screening of biological and chemical control agents.

Related:

• Colony Collapse Disorder

Emerging and reemerging infectious diseases are increasing worldwide and represent a major public health concern. One class of emerging human and animal diseases is caused by fungi. A new study examines an outbreak of a fungal infection, Cryptococcus gattii, in the Pacific Northwest of the United States. This fungus has been considered a tropical fungus, but emerged to cause an outbreak in the temperate climes of Vancouver Island in 1999 that is now causing disease in humans and animals in the United States. Because of the way an Oregon-specific strain of the fungus is reproducing and spreading, it will likely move into California and other adjacent areas. This novel fungus is worrisome because it appears to be a threat to otherwise healthy people. Typically, we more often see this fungal disease associated with transplant recipients and HIV-infected patients, but that is not what we are seeing in this case. VGIIc, the new Oregon strain, has yielded dozens of isolates from many specimens, including domesticated animals like cats, dogs and sheep – even an unlucky alpaca. Most of those are nonmigratory animals, which suggests that the animals probably didn’t bring the pathogen from some other region but, rather, acquired it locally. Using molecular techniques, the geneticists uncovered clues that showed the Oregon-only fungal strain most likely arose recently, parallel to the outbreak of C. gattii that began in Canada in 1999 that has now spread into Washington and Oregon.

The researchers found that the novel genotype (VGIIc) is now a major source of C. gattii illness in Oregon. Because C. gattii types had previously been found in tropical areas, the authors speculate that environmental changes may be responsible for the evolution and emergence of this pathogen. Determining the exact origin of the VGIIc type is difficult, and sampling thus far has failed to turn up isolates in Oregon soil, water or trees. The mortality rate for recent C. gattii cases in the Pacific Northwest is running at approximately 25 percent, or 5 out of 21 cases analyzed in the United States, compared to a mortality rate of 8.7 percent of 218 cases in British Columbia, Canada. Most C. gattii infections follow a more complicated clinical course in people than does the more common Cryptococcus neoformans. Symptoms can appear two to several months after exposure, and while most people never develop symptoms, those infected may have a cough lasting weeks, sharp chest pain, shortness of breath, headache (related to meningitis), fever, night time sweats and weight loss. In animals the symptoms are a runny nose, breathing problems, nervous system problems and raised bumps under the skin. While C. gattii can be treated, it cannot be prevented; there is no vaccine. Because the strain is so virulent when it infects some humans and animals, the researchers are calling for greater awareness and vigilance in testing. Some strains of C. gattii are not more virulent than C. neoformans, for example, but doctors need to know what type they are dealing with.

Emergence and Pathogenicity of Highly Virulent Cryptococcus gattii Genotypes in the Northwest United States. PLoS Pathog 6(4): e1000850. doi:10.1371/journal.ppat.1000850
Cryptococcus gattii causes life-threatening disease in otherwise healthy hosts and to a lesser extent in immunocompromised hosts. The highest incidence for this disease is on Vancouver Island, Canada, where an outbreak is expanding into neighboring regions including mainland British Columbia and the United States. This outbreak is caused predominantly by C. gattii molecular type VGII, specifically VGIIa/major. In addition, a novel genotype, VGIIc, has emerged in Oregon and is now a major source of illness in the region. Through molecular epidemiology and population analysis of MLST and VNTR markers, we show that the VGIIc group is clonal and hypothesize it arose recently. The VGIIa/IIc outbreak lineages are sexually fertile and studies support ongoing recombination in the global VGII population. This illustrates two hallmarks of emerging outbreaks: high clonality and the emergence of novel genotypes via recombination. In macrophage and murine infections, the novel VGIIc genotype and VGIIa/major isolates from the United States are highly virulent compared to similar non-outbreak VGIIa/major-related isolates. Combined MLST-VNTR analysis distinguishes clonal expansion of the VGIIa/major outbreak genotype from related but distinguishable less-virulent genotypes isolated from other geographic regions. Our evidence documents emerging hypervirulent genotypes in the United States that may expand further and provides insight into the possible molecular and geographic origins of the outbreak.

Related:

• Color me bad – microbial pigments as virulence factors
• All About Fungi: Part 1
• All About Fungi: Infection
• How human pathogenic fungi sense and adapt to pH

Whether it is in the setting of disease or in a healthy state, the human body contains a diverse range of microorganisms, including bacteria and fungi. The interactions between these taxonomically diverse microorganisms are highly dynamic and dependent on a multitude of microorganism and host factors. Human disease can develop from an imbalance between commensal bacteria and fungi or from invasion of particular host niches by opportunistic bacterial and fungal pathogens. This Review describes the clinical and molecular characteristics of bacterial–fungal interactions that are relevant to human disease.

Medically important bacterial–fungal interactions. 2010 Nature Reviews Microbiology 8, 340-349 doi:10.1038/nrmicro2313

Related:

• All About Fungi: Part 1
• All About Fungi: Infection
• How human pathogenic fungi sense and adapt to pH

Actinobacteria and filamentous fungi are just two examples of organisms that use cell elongation for growth. Mathematical models have been used to describe species-specific and more generic polarized growth. In this article in Microbiology Today (pdf) Fordyce Davidson suggests that multi-scale modelling could be the most effective approach to help us understand this morphological phenomenon:

Growth by cell elongation is a morphological process that transcends taxonomic kingdoms. Examples include hyphal tip growth in actinobacteria and filamentous fungi, plant root-hair formation and the development of neurons in animals. Such structures have developed almost certainly because they afford an evolutionary advantage – producing a growth habit well-suited to physically complex environments, facilitating the (internal) redeployment of nutrients or enabling the transfer of information over long spatial scales. The biology involved in producing this polarized growth form is clearly very different in plant, bacterial, fungal or mammalian cells. But its ubiquitous nature suggests that certain ‘”rules” are being followed. Moreover, if we compare fungi and actinobacteria, the foci of this article, it is clear that these rules are scalable: tip growth is similar, irrespective of the orders of magnitude difference in cell size. It appears that these rules form a blueprint for polarized growth.

Related:

• All About Fungi: Part 1
• Vesicular transport across the fungal cell wall

Invasive fungal infections are an increasing threat to human health. In the developed world, these infections predominantly occur in increasingly aggressive immunosuppressive therapies. The overall mortality for invasive diseases caused by Candida spp. and Aspergillus spp. is 30–50%, despite the advent of new diagnostic and therapeutic strategies. In the developing world, there are 1 million cases of cryptococcal disease per year, resulting in 675,000 deaths. Allergic fungal syndromes are increasingly recognised. Continued efforts are required to improve the often suboptimal therapeutic outcomes associated with fungal infections.

The high degree of phylogenetic relatedness between fungi and humans means that there are relatively few differential targets to be exploited for antifungal drug development. Fungi are involved in an interminable struggle for survival with each other and with other microbes. They produce a vast array of extracellular enzymes and secondary metabolites to counteract and digest the external world. Many antimicrobial agents have been isolated from fungi themselves. The best example is penicillin, which was isolated from Penicillium notatum (now Penicillium chrysogenum) by Fleming, and later purified for medical use by Florey and Chain. Similarly, the echinocandins, a novel class of antifungal compounds now in widespread clinical use, are semisynthetic derivatives of fungal-derived cyclic hexapeptides. Currently, five classes of antifungal agents are used orally or intravenously for the treatment of fungal infections in humans: polyenes, pyrimidine analogues, allylamines, azoles and the echinocandins. Each antifungal compound has advantages and limitations related to its spectrum of activity, route of administration, drug interactions and toxicity profile.

This review describes the role and limitations of these agents for the treatment of the most common and medically important syndromes, and provides a perspective on the current status of drug therapy for invasive fungal diseases, together with priorities for the future development of novel compounds. Key opportunities for new drugs include production of orally bioavailable agents for the treatment of invasive aspergillosis, invasive candidiasis, cryptococcal meningitis and mucosal and urinary Candida infections. Orally bioavailable agents for the treatment of chronic pulmonary and allergic aspergillosis are also required, as well as new potent drugs against a range of medically important moulds. Antifungal resistance is a problem in certain contexts, but is generally less of a problem than bacterial infections. Earlier and more complete mycological diagnosis and improvements in underlying risk estimation will improve outcomes.

Therapy for fungal diseases: opportunities and priorities. Trends Microbiol. March 5, 2010

Related:

• All About Fungi: Part 1
• All About Fungi: Infection

In 1518, one of the strangest epidemics in recorded history struck the city of Strasbourg. Hundreds of people were seized by an irresistible urge to dance, hop and leap into the air. In houses, halls and public spaces, as fear paralyzed the city and the members of the elite despaired, the dancing continued with mindless intensity. Seldom pausing to eat, drink or rest, many of them danced for days or even weeks. And before long, the chronicles agree, dozens were dying from exhaustion. What was it that could have impelled as many as 400 people to dance, in some cases to death?

Medieval dancing epidemics were not unrelated events: they were linked both in time and space. Every one of the ten or so outbreaks between the late 1300s and 1518 happened along the Rhine and Mosel rivers. In 1374, for instance, the crazed dance gradually spread out from an epicentre around Aachen, Liege and Maastricht to neighbouring towns such as Ghent, Utrecht, Metz, Trier and, eventually, Strasbourg. Moreover, outbreaks of compulsive dancing virtually always struck in or close to places affected by earlier outbreaks. Maastricht, Trier, Zurich and Strasbourg each experienced two or more episodes. There are also several reports of compulsive dancing after 1518. All of these, crucially, took place close to the Rhine, and all but one within a short ride of Strasbourg itself.

How can we explain this striking epidemiological picture? One suggestion is that wild dancing formed part of the ecstatic ritual of a heretical sect, an energetic counterpart of the flagellant’s cult. There are two main difficulties with this theory. First, in lucid moments the dancers implored bystanders and priests to come to their aid. There is absolutely no evidence that the dancers wanted to dance. On the contrary, they expressed fear and desperation. Second, the authorities consistently saw the afflicted not as heretics but as the victims of diabolical possession or divine curse, and treated them accordingly. The dancers were subject to exorcisms or sent on pilgrimages. Never were they hauled before the inquisition.

Other authors have sought a chemical or biological origin for the dancing mania, and the chief contender has been ergot, a mould that grows on the stalks of damp rye. While seductively simple, this hypothesis is untenable. The chemicals contained in ergot do not allow for sustained dancing. They can certainly trigger violent convulsions and delusions, but not coordinated movements that last for days. Yet while the dancers were free from ergot, they almost certainly were delirious. Only in an altered state of consciousness could they have tolerated such extreme fatigue and the searing pain of sore, swollen and bleeding feet. Moreover, witnesses consistently spoke of the victims as being entranced, seeing terrifying visions and behaving with wild, crazy abandon. So what could have plunged hundreds of people into trances so deep that remorseless dancing became possible? Psychologists, neurologists and anthropologists have identified severe psychological distress as a factor increasing the likelihood of an individual entering an altered state. It is unlikely to be a coincidence, therefore, that in the year 1518 many people in Strasbourg were experiencing truly exceptional levels of hunger and mental anguish.

In a spin: the mysterious dancing epidemic of 1518. Endeavour. 2008 32(3): 117-121. doi: 10.1016/j.endeavour.2008.05.001