Non-systemic transmission of tick-borne diseases: a network approach

Tick-Borne diseases can be transmitted via non-systemic (NS) transmission. This occurs when tick gets the infection by co-feeding with infected ticks on the same host resulting in a direct pathogen transmission between the vectors, without infecting the host. This transmission is peculiar, as it does not require any systemic infection of the host. The NS transmission is the main efficient transmission for the persistence of the Tick-Borne Encephalitis virus in nature. By describing the heterogeneous ticks aggregation on hosts through a \hyphenation{dynamical} bipartite graphs representation, we are able to mathematically define the NS transmission and to depict the epidemiological conditions for the pathogen persistence. Despite the fact that the underlying network is largely fragmented, analytical and computational results show that the larger is the variability of the aggregation, and the easier is for the pathogen to persist in the population.Comment: 15 pages, 4 figures, to be published in Communications in Nonlinear Science and Numerical Simulatio

Clinical Persistence of Chlamydia trachomatis Sexually Transmitted Strains Involves Novel Mutations in the Functional αββα Tetramer of the Tryptophan Synthase Operon.

Clinical persistence of Chlamydia trachomatis (Ct) sexually transmitted infections (STIs) is a major public health concern. In vitro persistence is known to develop through interferon gamma (IFN-γ) induction of indoleamine 2,3-dioxygenase (IDO), which catabolizes tryptophan, an essential amino acid for Ct replication. The organism can recover from persistence by synthesizing tryptophan from indole, a substrate for the enzyme tryptophan synthase. The majority of Ct strains, except for reference strain B/TW-5/OT, contain an operon comprised of α and β subunits that encode TrpA and TrpB, respectively, and form a functional αββα tetramer. However, trpA mutations in ocular Ct strains, which are responsible for the blinding eye disease known as trachoma, abrogate tryptophan synthesis from indole. We examined serial urogenital samples from a woman who had recurrent Ct infections over 4 years despite antibiotic treatment. The Ct isolates from each infection episode were genome sequenced and analyzed for phenotypic, structural, and functional characteristics. All isolates contained identical mutations in trpA and developed aberrant bodies within intracellular inclusions, visualized by transmission electron microscopy, even when supplemented with indole following IFN-γ treatment. Each isolate displayed an altered αββα structure, could not synthesize tryptophan from indole, and had significantly lower trpBA expression but higher intracellular tryptophan levels compared with those of reference Ct strain F/IC-Cal3. Our data indicate that emergent mutations in the tryptophan operon, which were previously thought to be restricted only to ocular Ct strains, likely resulted in in vivo persistence in the described patient and represents a novel host-pathogen adaptive strategy for survival.IMPORTANCE Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterium with more than 131 million cases occurring annually worldwide. Ct infections are often asymptomatic, persisting for many years despite treatment. In vitro recovery from persistence occurs when indole is utilized by the organism's tryptophan synthase to synthesize tryptophan, an essential amino acid for replication. Ocular but not urogenital Ct strains contain mutations in the synthase that abrogate tryptophan synthesis. Here, we discovered that the genomes of serial isolates from a woman with recurrent, treated Ct STIs over many years were identical with a novel synthase mutation. This likely allowed long-term in vivo persistence where active infection resumed only when tryptophan became available. Our findings indicate an emerging adaptive host-pathogen evolutionary strategy for survival in the urogenital tract that will prompt the field to further explore chlamydial persistence, evaluate the genetics of mutant Ct strains and fitness within the host, and their implications for disease pathogenesis

Interplay of network dynamics and ties heterogeneity on spreading dynamics

The structure of a network dramatically affects the spreading phenomena unfolding upon it. The contact distribution of the nodes has long been recognized as the key ingredient in influencing the outbreak events. However, limited knowledge is currently available on the role of the weight of the edges on the persistence of a pathogen. At the same time, recent works showed a strong influence of temporal network dynamics on disease spreading. In this work we provide an analytical understanding, corroborated by numerical simulations, about the conditions for infected stable state in weighted networks. In particular, we reveal the role of heterogeneity of edge weights and of the dynamic assignment of weights on the ties in the network in driving the spread of the epidemic. In this context we show that when weights are dynamically assigned to ties in the network an heterogeneous distribution is able to hamper the diffusion of the disease, contrary to what happens when weights are fixed in time.Comment: 10 pages, 10 figure

Human mobility networks and persistence of rapidly mutating pathogens

Rapidly mutating pathogens may be able to persist in the population and reach an endemic equilibrium by escaping hosts' acquired immunity. For such diseases, multiple biological, environmental and population-level mechanisms determine the dynamics of the outbreak, including pathogen's epidemiological traits (e.g. transmissibility, infectious period and duration of immunity), seasonality, interaction with other circulating strains and hosts' mixing and spatial fragmentation. Here, we study a susceptible-infected-recovered-susceptible model on a metapopulation where individuals are distributed in subpopulations connected via a network of mobility flows. Through extensive numerical simulations, we explore the phase space of pathogen's persistence and map the dynamical regimes of the pathogen following emergence. Our results show that spatial fragmentation and mobility play a key role in the persistence of the disease whose maximum is reached at intermediate mobility values. We describe the occurrence of different phenomena including local extinction and emergence of epidemic waves, and assess the conditions for large scale spreading. Findings are highlighted in reference to previous works and to real scenarios. Our work uncovers the crucial role of hosts' mobility on the ecological dynamics of rapidly mutating pathogens, opening the path for further studies on disease ecology in the presence of a complex and heterogeneous environment.Comment: 29 pages, 7 figures. Submitted for publicatio

Enteropathogen survival in soil from different land-uses is predominantly regulated by microbial community composition

peer-reviewedMicrobial enteropathogens can enter the environment via landspreading of animal slurries and manures. Biotic interactions with the soil microbial community can contribute to their subsequent decay. This study aimed to determine the relative impact of biotic, specifically microbial community structure, and physico-chemical properties associated with soils derived from 12 contrasting land-uses on enteropathogen survival. Phenotypic profiles of microbial communities (via phospholipid fatty acid (PLFA) profiling), and total biomass (by fumigation-extraction), in the soils were determined, as well as a range of physicochemical properties. The persistence of Salmonella Dublin, Listeria monocytogenes, and Escherichia coli was measured over 110 days within soil microcosms. Physicochemical and biotic data were used in stepwise regression analysis to determine the predominant factor related to pathogen-specific death rates. Phenotypic structure, associated with a diverse range of constituent PLFAs, was identified as the most significant factor in pathogen decay for S. Dublin, L. monocytogenes, non-toxigenic E. coli O157 but not for environmentally-persistent E. coli. This demonstrates the importance of entire community-scale interactions in pathogen suppression, and that such interactions are context-specific

Phenotypic and Genotypic Characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) Related to Persistent Endovascular Infection.

Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (PB) represents an important subset of S. aureus infection and correlates with poor clinical outcomes. MRSA isolates from patients with PB differ significantly from those of resolving bacteremia (RB) with regard to several in vitro phenotypic and genotypic profiles. For instance, PB strains exhibit less susceptibility to cationic host defense peptides and vancomycin (VAN) killing under in vivo-like conditions, greater damage to endothelial cells, thicker biofilm formation, altered growth rates, early activation of many global virulence regulons (e.g., sigB, sarA, sae and agr) and higher expression of purine biosynthesis genes (e.g., purF) than RB strains. Importantly, PB strains are significantly more resistant to VAN treatment in experimental infective endocarditis as compared to RB strains, despite similar VAN minimum inhibitory concentrations (MICs) in vitro. Here, we review relevant phenotypic and genotypic characteristics related to the PB outcome. These and future insights may improve our understanding of the specific mechanism(s) contributing to the PB outcome, and aid in the development of novel therapeutic and preventative measures against this life-threatening infection

Salmonella Typhimurium resides largely as an extracellular pathogen in porcine tonsils, independently of biofilm-associated genes csgA, csgD and adrA

In European countries, Salmonella enterica subspecies enterica serovar Typhimurium (Salmonella Typhimurium) is the serovar most frequently isolated from slaughter pigs1. Porcine carcass contamination with Salmonella Typhimurium can largely be attributed to persistently infected pigs. Even though tonsils are a predilection site for Salmonella persistence in pigs, virulence mechanisms necessary for cell invasion and intracellular survival do not contribute to tonsillar colonization2, suggesting that Salmonella Typhimurium resides mainly extracellularly in porcine tonsils. Biofilm formation is a mechanism used by several bacteria to survive in an extracellular context or in hostile environments3. The role of biofilm formation in Salmonella Typhimurium persistence in pigs is still unknown. It was the aim of the present study to determine whether Salmonella Typhimurium persists intracellularly or extracellularly in tonsils of pigs. Additionally, the role of biofilm formation in persistence of Salmonella Typhimurium in porcine tonsils was determined