HCMV I’m a little out of date with my cytomegalovirus (CMV) knowledge. As I currently have a student working on a project on virus infections in pregnancy, this short review – focussing on new treatment options for cytomegalovirus infection, recent clinical trials and bone marrow transplantation, congenital infections and interventions during pregnancy – is most welcome.

Cytomegalovirus. Curr Opin Infect Dis. 08 Oct 2014. doi: 10.1097/QCO.0000000000000107
Three double-blind randomized placebo-controlled phase 2 proof-of-concept studies have each identified a novel antiviral drug with activity against CMV infection in bone marrow transplant patients. One of these (brincidofovir) inhibits the DNA polymerase that is the target of the currently licensed drug ganciclovir. Another new drug (maribavir) inhibits a protein kinase which, coincidentally, is the enzyme responsible for activating ganciclovir through phosphorylation. The third drug (letermovir) inhibits the terminase enzyme complex responsible for packaging unit length DNA into assembling virions.In addition, in a double-blind randomized placebo-controlled trial in neonates with symptomatic congenital CMV infection, a 6-month course of valganciclovir was superior to the standard 6-week course of the same drug. In pregnant women with primary CMV infection, administration of hyperimmune immunoglobulin did not significantly reduce transmission of CMV across the placenta. The ability to diagnose CMV infections reliably in different clinical settings through application of molecular laboratory methods has ushered in new ways of evaluating potential new treatments for CMV. Several of these may help control the diseases caused by this important human pathogen.

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Viroids: Survivors from the RNA World?

Viroid A new review in Annual Review of Microbiology gives an excellent introduction to viroids.


  • Introduction: Why The Need For An RNA World?
  • Viroids: Essential Features
  • Discovery of a Subviral World
  • Structure: Small Circular RNAs with Compact Folding
  • Replication: Rolling-Circle Mechanism Catalyzed by Enzymes and Ribozymes
  • Sequence Diversity
  • Viroid-Related Replicons
  • Viroid-Like Satellite RNAs
  • Retroviroid-Like Elements
  • Hepatitis δ virus
  • Why Are Viroids And Viroid-Related Replicons Regarded As Survivors Of The RNA World?
  • Early Speculations on the Origin of Viroids
  • Circular RNAs: Relics of Precellular Evolution?
  • Viroid-Related Replicons
  • Summary


Viroids: Survivors from the RNA World? (2014) Annual Review of Microbiology, 68(1): 395-414. doi: 10.1146/annurev-micro-091313-103416


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The Flawed Prokaryote

Bacterial origins There are two types of biologist – those who think that prokaryotes exist and those who don’t.

The simple binary divide between prokaryotes and eukarotes is an old (19th Century) idea. Splitting all life forms into two headings (let’s leave viruses out of this for now) is seductive. The problem is that this old idea – still trotted out in textbooks – doesn’t stand up to molecular data. Even though we only need three domains (bacteria, eukarya and archaea) to account for scientific observations, the old prokaryote-eukaryote idea just won’t die. Think about that when you’re writing your essays…


Pace, N.R. (2006) Time for a change. Nature, 441(7091), 289-289. doi:10.1038/441289a

Close Encounters of the Third Domain: The Emerging Genomic View of Archaeal Diversity and Evolution. Archaea, 2013.

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Welcome to new microbiology students

MicrobiologyBytes MicrobiologyBytes has been explaining the latest news about microbiology for nearly ten years and is read by thousands of people worldwide each month. I hope that you will become one of them. You can read MicrobiologyBytes on this website, or if you prefer, get notification of new items on Facebook or Twitter or by email (click the Follow button top right). And it’s all free and always will be.

Over the years, I have built up collections of thousands of microbiology images such as bacteria, viruses and fungi which you’re free to use as long as you remember to say where you got them from.

So whether you’re a student (or a teacher) of microbiology, welcome to MicrobiologyBytes. Remember to ask lots of questions, and most importantly – enjoy learning. And if you, like me, are not so new to microbiology, thanks for sticking around. i’d appreciate it if you left me a brief comment on how you use MicrobiologyBytes and if there’s anything else you’d lie to see here – because while the content is microbiology, MicrobiologyBytes is really all about you.


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Whole Genome Sequencing for Outbreak Detection of Salmonella enterica

Salmonella typhimurium Salmonella bacteria are a common cause of infectious disease in human and animals. Salmonella is classically divided into species S. bongori and S. enterica – which is in turn further divided into more than 2,500 different serotypes. However, only a limited number of serovars that are responsible for most infections. In Europe, the most prevalent S. enterica serovars isolated from humans are Enteritidis and Typhimurium, responsible for over 75% of the human cases of salmonellosis.

In order to understand the epidemiology and implement control programs, reliable and rapid sub-typing is essential. Different typing methods are commonly used as a central part of the detection and investigation of Salmonella outbreaks, for instance, serotyping, phage typing, pulse-field gel electrophoresis (PFGE) and multilocus variable number of tandem repeat analysis (MLVA). PFGE has become the standard for epidemiological investigations of foodborne bacterial pathogens including Salmonella. A drawback of PFGE is that it is unable to separate very closely related strains because the low rate of genetic variation does not significantly impact the electrophoretic mobility of a restriction fragment.

During recent years the cost of whole genome sequencing (WGS) has decreased dramatically and the technology becomes increasingly available for routine use around the world. The speed of sequencing is decreasing from several days or weeks to perhaps hours for a bacterial genome in the near future. This combination of low cost and high speed opens an opportunity for WGS to become very useful and practical in bacterial infection studies including the routine use in diagnostic and public health microbiology.

A new study evaluates WGS for outbreak typing of S. enterica and compares it to results obtained using the conventional typing method, PFGE. The results show that WGS alone is insufficient to determine whether strains are related or un-related to outbreaks. This still requires the combination of epidemiological data and whole genome sequencing results.

Evaluation of Whole Genome Sequencing for Outbreak Detection of Salmonella enterica. (2014) PLoS ONE 9(2): e87991. doi: 10.1371/journal.pone.0087991
Salmonella enterica is a common cause of minor and large food borne outbreaks. To achieve successful and nearly ‘real-time’ monitoring and identification of outbreaks, reliable sub-typing is essential. Whole genome sequencing (WGS) shows great promises for using as a routine epidemiological typing tool. Here we evaluate WGS for typing of S. Typhimurium including different approaches for analyzing and comparing the data. A collection of 34 S. Typhimurium isolates was sequenced. This consisted of 18 isolates from six outbreaks and 16 epidemiologically unrelated background strains. In addition, 8 S. Enteritidis and 5 S. Derby were also sequenced and used for comparison. A number of different bioinformatics approaches were applied on the data; including pan-genome tree, k-mer tree, nucleotide difference tree and SNP tree. The outcome of each approach was evaluated in relation to the association of the isolates to specific outbreaks. The pan-genome tree clustered 65% of the S. Typhimurium isolates according to the pre-defined epidemiology, the k-mer tree 88%, the nucleotide difference tree 100% and the SNP tree 100% of the strains within S. Typhimurium. The resulting outcome of the four phylogenetic analyses were also compared to PFGE reveling that WGS typing achieved the greater performance than the traditional method. In conclusion, for S. Typhimurium, SNP analysis and nucleotide difference approach of WGS data seem to be the superior methods for epidemiological typing compared to other phylogenetic analytic approaches that may be used on WGS. These approaches were also superior to the more classical typing method, PFGE. Our study also indicates that WGS alone is insufficient to determine whether strains are related or un-related to outbreaks. This still requires the combination of epidemiological data and whole genome sequencing results.

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Where will Ebola strike next?

Ebola risk Since the first outbreaks of Ebola virus disease in 1976, there have been numerous other outbreaks in humans across Africa with fatality rates ranging from 50% to 90%. Humans can become infected with the Ebola virus after direct contact with blood or bodily fluids from an infected person or animal. The virus also infects and kills other primates, though fruit bats are suspected to be the most likely carriers of the virus in the wild.

The largest recorded outbreak of Ebola virus disease is ongoing in West Africa: more people have been infected in this current outbreak than in all previous outbreaks combined. The current outbreak is also the first to occur in West Africa – which is outside the previously known range of the Ebola virus. A new paper in eLife updates predictions about where in Africa wild animals may harbour the virus and where the transmission of the virus from these animals to humans is possible.

Mapping the zoonotic niche of Ebola virus disease in Africa. (2014) eLife 3:e04395 doi: 10.7554/eLife.04395
Ebola virus disease (EVD) is a complex zoonosis that is highly virulent in humans. The largest recorded outbreak of EVD is ongoing in West Africa, outside of its previously reported and predicted niche. We assembled location data on all recorded zoonotic transmission to humans and Ebola virus infection in bats and primates (1976–2014). Using species distribution models, these occurrence data were paired with environmental covariates to predict a zoonotic transmission niche covering 22 countries across Central and West Africa. Vegetation, elevation, temperature, evapotranspiration, and suspected reservoir bat distributions define this relationship. At-risk areas are inhabited by 22 million people; however, the rarity of human outbreaks emphasises the very low probability of transmission to humans. Increasing population sizes and international connectivity by air since the first detection of EVD in 1976 suggest that the dynamics of human-to-human secondary transmission in contemporary outbreaks will be very different to those of the past.

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Recent developments linking retroviruses to human breast cancer

Retrovirus replication We have known for decades that viruses =can couse breast cancer in animals (Mouse Mammary Tumour Virus – MMTV). Evidence has been accumulating that retroviruses may play a part in human breast cancers. This short review summarizes iur prsent state fo knowledge.


Recent developments linking retroviruses to human breast cancer: infectious agent, enemy within or both? J Gen Virol. 12 Sep 2014. doi: 10.1099/vir.0.070631-0
Evidence is accumulating that one or more beta-retrovirus is associated with human breast cancer. Retroviruses can exist as an infectious (exogenous) virus or as a part of the genetic information of cells due to germline integration (endogenous). An exogenous virus with a genome that is highly homologous to mouse mammary tumor virus (MMTV) is gaining acceptance as possibly being associated with human breast cancer and recently furnished evidence is discussed in this article, as is the evidence for involvement of an endogenous human beta-retrovirus, HERV-K. Modes of interaction are also reviewed and linkage to APOBEC3 suggested.


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Streptococcus pneumoniae causes cardiac lesions

Streptococcus pneumoniae Hospitalization for community-acquired pneumonia carries a documented risk for adverse cardiac events. These occur during infection and contribute to elevated mortality rates in convalescent individuals up to a year after. A new paper describes a previously unrecognized pathogenic mechanism by which Streptococcus pneumoniae, the leading cause of community-acquired pneumonia, causes direct cardiotoxicity and forms microscopic bacteria-filled lesions within the heart.

Cardiac microlesions were detected in experimentally infected mice and rhesus macaques, as well as in heart sections from humans who succumbed to invasive pneumococcal disease. Cardiac microlesion formation required interaction of the bacterial adhesin CbpA with host laminin receptor and bacterial cell wall with platelet-activating factor receptor and also involved the pore-forming toxin pneumolysin. When infected mice were rescued with antibiotics, collagen deposition occurs at former lesion sites. Thus, microlesions and the scarring that occurs thereafter may explain why adverse cardiac events occur during and following pneumococcal disease.

Streptococcus pneumoniae Translocates into the Myocardium and Forms Unique Microlesions That Disrupt Cardiac Function. (2014) PLoS Pathog 10(9): e1004383. doi:10.1371/journal.ppat.1004383
Hospitalization of the elderly for invasive pneumococcal disease is frequently accompanied by the occurrence of an adverse cardiac event; these are primarily new or worsened heart failure and cardiac arrhythmia. Herein, we describe previously unrecognized microscopic lesions (microlesions) formed within the myocardium of mice, rhesus macaques, and humans during bacteremic Streptococcus pneumoniae infection. In mice, invasive pneumococcal disease (IPD) severity correlated with levels of serum troponin, a marker for cardiac damage, the development of aberrant cardiac electrophysiology, and the number and size of cardiac microlesions. Microlesions were prominent in the ventricles, vacuolar in appearance with extracellular pneumococci, and remarkable due to the absence of infiltrating immune cells. The pore-forming toxin pneumolysin was required for microlesion formation but Interleukin-1b was not detected at the microlesion site ruling out pneumolysin-mediated pyroptosis as a cause of cell death. Antibiotic treatment resulted in maturing of the lesions over one week with robust immune cell infiltration and collagen deposition suggestive of long-term cardiac scarring. Bacterial translocation into the heart tissue required the pneumococcal adhesin CbpA and the host ligands Laminin receptor (LR) and Platelet-activating factor receptor. Immunization of mice with a fusion construct of CbpA or the LR binding domain of CbpA with the pneumolysin toxoid L460D protected against microlesion formation. We conclude that microlesion formation may contribute to the acute and long-term adverse cardiac events seen in humans with IPD.


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What’s the diference between cow TB and human TB?

Mycobacterium tuberculosis In 1901, when Robert Koch proposed that the bacilli causing human and bovine tuberculosis were not identical, this view caused much controversy. 113 years later we know that the bovine tuberculosis agent, Mycobacterium bovis, together with other animal strains, forms a separate phylogenetic lineage apart from the human Mycobacterium tuberculosis lineages, but the molecular reasons why bovine and animal strains only play minor roles in human tuberculosis epidemiology remain unknown. A recent paper in PNAS uses genetic transfer and virulence experiments to show that specific mutations in a virulence regulator contribute to lower fitness and virulence of M. bovis and related strains for the human host, likely obstructing the capacity of causing overt disease needed for efficient human-to-human transmission.

Evolutionary history of tuberculosis shaped by conserved mutations in the PhoPR virulence regulator. (2014) PNAS USA 111(31): 11491–11496, doi: 10.1073/pnas.1406693111
Although the bovine tuberculosis (TB) agent, Mycobacterium bovis, may infect humans and cause disease, long-term epidemiological data indicate that humans represent a spill-over host in which infection with M. bovis is not self-maintaining. Indeed, human-to-human transmission of M. bovis strains and other members of the animal lineage of the tubercle bacilli is very rare. Here, we report on three mutations affecting the two-component virulence regulation system PhoP/PhoR (PhoPR) in M. bovis and in the closely linked Mycobacterium africanum lineage 6 (L6) that likely account for this discrepancy. Genetic transfer of these mutations into the human TB agent, Mycobacterium tuberculosis, resulted in down-regulation of the PhoP regulon, with loss of biologically active lipids, reduced secretion of the 6-kDa early antigenic target (ESAT-6), and lower virulence. Remarkably, the deleterious effects of the phoPR mutations were partly compensated by a deletion, specific to the animal-adapted and M. africanum L6 lineages, that restores ESAT-6 secretion by a PhoPR-independent mechanism. Similarly, we also observed that insertion of an IS6110 element upstream of the phoPR locus may completely revert the phoPR-bovis–associated fitness loss, which is the case for an exceptional M. bovis human outbreak strain from Spain. Our findings ultimately explain the long-term epidemiological data, suggesting that M. bovis and related phoPR-mutated strains pose a lower risk for progression to overt human TB, with major impact on the evolutionary history of TB.

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