Global analysis of gene expression reveals mRNA superinduction is required for the inducible immune response to a bacterial pathogen.

The inducible innate immune response to infection requires a concerted process of gene expression that is regulated at multiple levels. Most global analyses of the innate immune response have focused on transcription induced by defined immunostimulatory ligands, such as lipopolysaccharide. However, the response to pathogens involves additional complexity, as pathogens interfere with virtually every step of gene expression. How cells respond to pathogen-mediated disruption of gene expression to nevertheless initiate protective responses remains unclear. We previously discovered that a pathogen-mediated blockade of host protein synthesis provokes the production of specific pro-inflammatory cytokines. It remains unclear how these cytokines are produced despite the global pathogen-induced block of translation. We addressed this question by using parallel RNAseq and ribosome profiling to characterize the response of macrophages to infection with the intracellular bacterial pathogen Legionella pneumophila. Our results reveal that mRNA superinduction is required for the inducible immune response to a bacterial pathogen

Survival of Fecal Contamination Indicator Organisms in Soil

Soils amended with human or animal waste may result in pathogen contamination of ground and surface water. Because temperature has been shown to affect pathogen survival, two laboratory studies were conducted to evaluate the impact of extremes in temperature on bacterial and viral pathogen indicator die-off in soil. A Captina silt loam was amended with broiler litter (0.1 g/g dry soil), septic tank effluent, or Escherichia coli (ATCC 13706) culture (both at 0.04 and 0.1 mL/g dry soil in the two respective studies), incubated at 5 and 35°C, and analyzed over time to determine the number of fecal coliform, E. coli, and coliphage remaining. Pathogen indicator die-off rate constants (k) for all indicator- temperature-treatment combinations were determined by first-order kinetics. For all three pathogen indicators, die-off was significantly more rapid at 35°C than at 5°C. In both studies, fecal coliform die-off rates were not different from E. coli die-off rates across each temperature-treatment combination. Levels of these bacterial indicators appeared in a ratio of 1:0.94 with 95% confidence intervals at 0.89 and 0.99 in the E. coli- and litter-amended soils. Die-off of the viral indicator was significantly slower than the die-off of the bacterial indicators at 5°C in litter-amended soil. Die-off of the bacterial indicator, E. coli, in soil amended with E. coli culture was not significantly different than die-off in soil amended with broiler litter at 5 or 35°C in the two studies. Because the higher incubation temperature increased die-off rates for all three indicators, it is expected that the potential for contamination of ground and surface water decreases with increasing temperature

Effects of Noise on Ecological Invasion Processes: Bacteriophage-mediated Competition in Bacteria

Pathogen-mediated competition, through which an invasive species carrying and transmitting a pathogen can be a superior competitor to a more vulnerable resident species, is one of the principle driving forces influencing biodiversity in nature. Using an experimental system of bacteriophage-mediated competition in bacterial populations and a deterministic model, we have shown in [Joo et al 2005] that the competitive advantage conferred by the phage depends only on the relative phage pathology and is independent of the initial phage concentration and other phage and host parameters such as the infection-causing contact rate, the spontaneous and infection-induced lysis rates, and the phage burst size. Here we investigate the effects of stochastic fluctuations on bacterial invasion facilitated by bacteriophage, and examine the validity of the deterministic approach. We use both numerical and analytical methods of stochastic processes to identify the source of noise and assess its magnitude. We show that the conclusions obtained from the deterministic model are robust against stochastic fluctuations, yet deviations become prominently large when the phage are more pathological to the invading bacterial strain.Comment: 39 pages, 7 figure

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution

Host stress drives Salmonella recrudescence

Host stress is well known to result in flare-ups of many bacterial, viral and parasitic infections. The mechanism by which host stress is exploited to increase pathogen loads, is poorly understood. Here we show that Salmonella enterica subspecies enterica serovar Typhimurium employs a dedicated mechanism, driven by the scsA gene, to respond to the host stress hormone cortisol. Through this mechanism, cortisol increases Salmonella proliferation inside macrophages, resulting in increased intestinal infection loads in DBA/2J mice. ScsA directs overall Salmonella virulence gene expression under conditions that mimic the intramacrophagic environment of Salmonella, and stimulates the host cytoskeletal alterations that are required for increased Salmonella proliferation inside cortisol exposed macrophages. We thus provide evidence that in a stressed host, the complex interplay between a pathogen and its host endocrine and innate immune system increases intestinal pathogen loads to facilitate pathogen dispersal

Tissue Tropism in Host Transcriptional Response to Members of the Bovine Respiratory Disease Complex.

Bovine respiratory disease (BRD) is the most common infectious disease of beef and dairy cattle and is characterized by a complex infectious etiology that includes a variety of viral and bacterial pathogens. We examined the global changes in mRNA abundance in healthy lung and lung lesions and in the lymphoid tissues bronchial lymph node, retropharyngeal lymph node, nasopharyngeal lymph node and pharyngeal tonsil collected at the peak of clinical disease from beef cattle experimentally challenged with either bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Mannheimia haemolytica or Mycoplasma bovis. We identified signatures of tissue-specific transcriptional responses indicative of tropism in the coordination of host's immune tissue responses to infection by viral or bacterial infections. Furthermore, our study shows that this tissue tropism in host transcriptional response to BRD pathogens results in the activation of different networks of response genes. The differential crosstalk among genes expressed in lymphoid tissues was predicted to be orchestrated by specific immune genes that act as 'key players' within expression networks. The results of this study serve as a basis for the development of innovative therapeutic strategies and for the selection of cattle with enhanced resistance to BRD

How to rewire the host cell: A home improvement guide for intracellular bacteria.

Intracellular bacterial pathogens have developed versatile strategies to generate niches inside the eukaryotic cells that allow them to survive and proliferate. Making a home inside the host offers many advantages; however, intracellular bacteria must also overcome many challenges, such as disarming innate immune signaling and accessing host nutrient supplies. Gaining entry into the cell and avoiding degradation is only the beginning of a successful intracellular lifestyle. To establish these replicative niches, intracellular pathogens secrete various virulence proteins, called effectors, to manipulate host cell signaling pathways and subvert host defense mechanisms. Many effectors mimic host enzymes, whereas others perform entirely novel enzymatic functions. A large volume of work has been done to understand how intracellular bacteria manipulate membrane trafficking pathways. In this review, we focus on how intracellular bacterial pathogens target innate immune signaling, the unfolded protein response, autophagy, and cellular metabolism and exploit these pathways to their advantage. We also discuss how bacterial pathogens can alter host gene expression by directly modifying histones or hijacking the ubiquitination machinery to take control of several host signaling pathways

Friend and foe: factors influencing the movement of the bacterium Helicobacter pylori along the parasitism-mutualism continuum.

Understanding the transition of bacterial species from commensal to pathogen, or vice versa, is a key application of evolutionary theory to preventative medicine. This requires working knowledge of the molecular interaction between hosts and bacteria, ecological interactions among microbes, spatial variation in bacterial prevalence or host life history, and evolution in response to these factors. However, there are very few systems for which such broad datasets are available. One exception is the gram-negative bacterium, Helicobacter pylori, which infects upwards of 50% of the global human population. This bacterium is associated with a wide breadth of human gastrointestinal disease, including numerous cancers, inflammatory disorders, and pathogenic infections, but is also known to confer fitness benefits to its host both indirectly, through interactions with other pathogens, and directly. Outstanding questions are therefore why, when, and how this bacterium transitions along the parasitism-mutualism continuum. We examine known virulence factors, genetic predispositions of the host, and environmental contributors that impact progression of clinical disease and help define geographical trends in disease incidence. We also highlight the complexity of the interaction and discuss future therapeutic strategies for disease management and public health in light of the longstanding evolutionary history between the bacterium and its human host

Molecular Mechanisms Used by Salmonella to Evade the Immune System

Human and animal pathogens are able to circumvent, at least temporarily, the sophisticated immune defenses of their hosts. Several serovars of the Gram-negative bacterium Salmonella enterica have been used as models for the study of pathogen-host interactions. In this review we discuss the strategies used by Salmonella to evade or manipulate three levels of host immune defenses: physical barriers, innate immunity and adaptive immunity. During its passage through the digestive system, Salmonella has to face the acidic pH of the stomach, bile and antimicrobial peptides in the intestine, as well as the competition with resident microbiota. After host cell invasion, Salmonella manipulates inflammatory pathways and the autophagy process. Finally, Salmonella evades the adaptive immune system by interacting with dendritic cells, and T and B lymphocytes. Mechanisms allowing the establishment of persistent infections are also discussed.European Regional Development Fund SAF2013-46229-R, SAF2016-75365-