The macroecology of infectious diseases: a new perspective on global‐scale drivers of pathogen distributions and impacts

Identifying drivers of infectious disease patterns and impacts at the broadest scales of organisation is one of the most crucial challenges for modern science, yet answers to many fundamental questions remain elusive. These include what factors commonly facilitate transmission of pathogens to novel host species, what drives variation in immune investment among host species, and more generally what drives global patterns of parasite diversity and distribution? Here we consider how the perspectives and tools of macroecology, a field that investigates patterns and processes at broad spatial, temporal and taxonomic scales, are expanding scientific understanding of global infectious disease ecology. In particular, emerging approaches are providing new insights about scaling properties across all living taxa, and new strategies for mapping pathogen biodiversity and infection risk. Ultimately, macroecology is establishing a framework to more accurately predict global patterns of infectious disease distribution and emergence.     

Expanding the soil antibiotic resistome: exploring environmental diversity

Antibiotic resistance has largely been studied in the context of failure of the drugs in clinical settings. There is now growing evidence that bacteria that live in the environment (e.g. the soil) are multi-drug-resistant. Recent functional screens and the growing accumulation of metagenomic databases are revealing an unexpected density of resistance genes in the environment: the antibiotic resistome. This challenges our current understanding of antibiotic resistance and provides both barriers and opportunities for antimicrobial drug discovery.     

The RNase E of Escherichia coli is a membrane-binding protein

RNase E is an essential endoribonuclease involved in RNA processing and mRNA degradation. The N-terminal half of the protein encompasses the catalytic domain; the C-terminal half is the scaffold for the assembly of the multienzyme RNA degradosome. Here we identify and characterize 'segment-A', an element in the beginning of the non-catalytic region of RNase E that is required for membrane binding. We demonstrate in vitro that an oligopeptide corresponding to segment-A has the propensity to form an amphipathic alpha-helix and that it avidly binds to protein-free phospholipid vesicles. We demonstrate in vitro and in vivo that disruption of segment-A in full-length RNase E abolishes membrane binding. Taken together, our results show that segment-A is necessary and sufficient for RNase E binding to membranes. Strains in which segment-A has been disrupted grow slowly. Since in vitro experiments show that phospholipid binding does not affect the ribonuclease activity of RNase E, the slow-growth phenotype might arise from a defect involving processes such as accessibility to substrates or interactions with other membrane-bound machinery. This is the first report demonstrating that RNase E is a membrane-binding protein and that its localization to the inner cytoplasmic membrane is important for normal cell growth.     

Identification of diagnostic biomarkers for infection in premature neonates

Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P- and E-selectins, interleukin 2 soluble receptor alpha, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.     

Genetic diversity,genetic drift and mixed mating system in small subpopulations of <Emphasis Type="Italic">Dyckia ibiramensis</Emphasis>, a rare endemic bromeliad from Southern Brazil

Dyckia ibiramensis is a naturally rare, endemic and threatened bromeliad which occurs naturally on 4 km of rocky river outcroppings in Southern Brazil. For this study, subpopulations of the species were characterized based on size and genetics, to compile information for in situ and ex situ conservation strategies. A census of the rosettes was undertaken for each subpopulation and seven allozyme polymorphic loci were used to estimate genetic diversity and structure of adults and offspring and assess the mating system. In general, the subpopulations were small and most of the rosettes were aggregated into clumps. The species showed a high genetic diversity ([^(H)]_e = 0.219 \hat{H}_{e} = 0.219 ) and significant fixation index ([^(f)] = 0.642, \hat{f} = 0.642, P ≤ 0.05). The estimate of differentiation among all adult subpopulations indicate pronounced genetic structure ([^(G)]^￠_ST = 0.674 \hat{G}^{\prime}_{ST} = 0.674 ). D. ibiramensis has a mixed mating system and multilocus outcrossing rates [^(t)]_m \hat{t}_{m} were variable between subpopulations. This study demonstrates the importance of in situ preservation of all subpopulations for the maintenance of species diversity. For effective ex situ conservation, it would be necessary to collect seeds from 52 to 99 seed-rosettes, depending on the target population.     

Does the niche breadth or trade‐off hypothesis explain the abundance–occupancy relationship in avian Haemosporidia?

Two hypotheses have been proposed to explain the abundance–occupancy relationship (AOR) in parasites. The niche breadth hypothesis suggests that host generalists are more abundant and efficient at colonizing different host communities than specialists. The trade‐off hypothesis argues that host specialists achieve high density across their hosts' ranges, whereas generalists incur the high cost of adaptation to diverse immuno‐defence systems. We tested these hypotheses using 386 haemosporidian cytochrome‐b lineages (1894 sequences) recovered from 2318 birds of 103 species sampled in NW Africa, NW Iberia, W Greater Caucasus and Transcaucasia. The number of regions occupied by lineages was associated with their frequency suggesting the presence of AOR in avian Haemosporidia. However, neither hypothesis provided a better explanation for the AOR. Although the host generalist Plasmodium SGS1 was over three times more abundant than other widespread lineages, both host specialists and generalists were successful in colonizing all study regions and achieved high overall prevalence.     

Cross talk between MyD88 and focal adhesion kinase pathways

Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase involved in signaling downstream of integrins, linking bacterial detection, cell entry, and initiation of proinflammatory response through MAPKs and NF-kappaB activation. In this study, using protein I/II from Streptococcus mutans as a model activator of FAK, we investigated the potential link between FAK and TLR pathways. Using macrophages from TLR- or MyD88-deficient mice, we report that MyD88 plays a major role in FAK-dependent protein I/II-induced cytokine release. However, response to protein I/II stimulation was independent of TLR4, TLR2, and TLR6. The data suggest that there is a cross talk between FAK and MyD88 signaling pathways. Moreover, MyD88-dependent, LPS-induced IL-6 secretion by human and murine fibroblasts required the presence of FAK, confirming that MyD88 and FAK pathways are interlinked.