Susceptibility to Ticks and Lyme Disease Spirochetes Is Not Affected in Mice Coinfected with Nematodes

Small rodents serve as reservoir hosts for tick-borne pathogens, such as the spirochetes causing Lyme disease. Whether natural coinfections with other macroparasites alter the success of tick feeding, antitick immunity, and the host's reservoir competence for tick-borne pathogens remains to be determined. In a parasitological survey of wild mice in Berlin, Germany, approximately 40% ofIxodes ricinus-infested animals simultaneously harbored a nematode of the genusHeligmosomoides. We therefore aimed to analyze the immunological impact of the nematode/tick coinfection as well as its effect on the tick-borne pathogenBorrelia afzelii. Hosts experimentally coinfected withHeligmosomoides polygyrusand larval/nymphalI. ricinusticks developed substantially stronger systemic type 2 T helper cell (Th2) responses, on the basis of the levels of GATA-3 and interleukin-13 expression, than mice infected with a single pathogen. During repeated larval infestations, however, anti-tick Th2 reactivity and an observed partial immunity to tick feeding were unaffected by concurrent nematode infections. Importantly, the strong systemic Th2 immune response in coinfected mice did not affect susceptibility to tick-borneB. afzelii. An observed trend for decreased local and systemic Th1 reactivity againstB. afzeliiin coinfected mice did not result in a higher spirochete burden, nor did it facilitate bacterial dissemination or induce signs of immunopathology. Hence, this study indicates that strong systemic Th2 responses in nematode/tick-coinfected house mice do not affect the success of tick feeding and the control of the causative agent of Lyme disease.

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Cyclic di-GMP Modulates Gene Expression in Lyme Disease Spirochetes at the Tick-Mammal Interface To Promote Spirochete Survival during the Blood Meal and Tick-to-Mammal Transmission

Infection and Immunity ◽

10.1128/iai.00315-15 ◽

2015 ◽

Vol 83 (8) ◽

pp. 3043-3060 ◽

Cited By ~ 39

Author(s):

Melissa J. Caimano ◽

Star Dunham-Ems ◽

Anna M. Allard ◽

Maria B. Cassera ◽

Melisha Kenedy ◽

...

Keyword(s):

Gene Regulation ◽

Lyme Disease ◽

Blood Meal ◽

Cell Envelope ◽

Glycerol Metabolism ◽

Two Component System ◽

Tick Feeding ◽

Content Type ◽

Glycerol Uptake ◽

Enzootic Cycle

Borrelia burgdorferi, the Lyme disease spirochete, couples environmental sensing and gene regulation primarily via the Hk1/Rrp1 two-component system (TCS) and Rrp2/RpoN/RpoS pathways. Beginning with acquisition, we reevaluated the contribution of these pathways to spirochete survival and gene regulation throughout the enzootic cycle. Live imaging ofB. burgdorfericaught in the act of being acquired revealed that the absence of RpoS and the consequent derepression of tick-phase genes impart a Stay signal required for midgut colonization. In addition to the behavioral changes brought on by the RpoS-off state, acquisition requires activation of cyclic di-GMP (c-di-GMP) synthesis by the Hk1/Rrp1 TCS;B. burgdorferilacking either component is destroyed during the blood meal. Prior studies attributed this dramatic phenotype to a metabolic lesion stemming from reduced glycerol uptake and utilization. In a head-to-head comparison, however, theB. burgdorferiΔglpmutant had a markedly greater capacity to survive tick feeding thanB. burgdorferiΔhk1or Δrrp1mutants, establishing unequivocally that glycerol metabolism is only one component of the protection afforded by c-di-GMP. Data presented herein suggest that the protective response mediated by c-di-GMP is multifactorial, involving chemotactic responses, utilization of alternate substrates for energy generation and intermediary metabolism, and remodeling of the cell envelope as a means of defending spirochetes against threats engendered during the blood meal. Expression profiling of c-di-GMP-regulated genes through the enzootic cycle supports our contention that the Hk1/Rrp1 TCS functions primarily, if not exclusively, in ticks. These data also raise the possibility that c-di-GMP enhances the expression of a subset of RpoS-dependent genes during nymphal transmission.

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Seasonal Prevalence of Lyme Disease Spirochetes in a Heterothermic Mammal, the Edible Dormouse (Glis glis)

Applied and Environmental Microbiology ◽

10.1128/aem.00251-14 ◽

2014 ◽

Vol 80 (12) ◽

pp. 3615-3621 ◽

Cited By ~ 8

Author(s):

Joanna Fietz ◽

Jürgen Tomiuk ◽

Franz-Rainer Matuschka ◽

Dania Richter

Keyword(s):

Lyme Disease ◽

Reservoir Host ◽

Glis Glis ◽

Content Type ◽

Transmission Cycle ◽

Western Germany ◽

Edible Dormice ◽

Study Sites ◽

Reservoir Hosts

ABSTRACTIn Europe, dormice serve as competent reservoir hosts for particular genospecies of the tick-borne agent of Lyme disease (LD) and seem to support them more efficiently than do mice or voles. The longevity of edible dormice (Glis glis) and their attractiveness for ticks may result in a predominance of LD spirochetes in ticks questing in dormouse habitats. To investigate the role of edible dormice in the transmission cycle of LD spirochetes, we sampled skin tissue from the ear pinnae of dormice inhabiting five different study sites in south western Germany. Of 501 edible dormice, 12.6% harbored DNA of LD spirochetes. Edible dormice were infected most frequently with the pathogenic LD spirocheteBorrelia afzelii. The DNA ofB. gariniiandB. bavariensiswas detected in ca. 0.5% of the examined individuals. No spirochetal DNA was detectable in the skin of edible dormice until July, 6 weeks after they generally start to emerge from their obligate hibernation. Thereafter, the prevalence of spirochetal DNA in edible dormice increased during the remaining period of their 4 to 5 months of activity, reaching nearly 40% in September. Males were more than four times more likely to harbor LD spirochetes than females, and yearlings were almost twice more likely to be infected than adults. The seasonality of the prevalence of LD spirochetes in edible dormice was pronounced and may affect their role as a reservoir host in respect to other hosts.

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The Factor H-Binding Site of CspZ as a Protective Target against Multistrain, Tick-Transmitted Lyme Disease

Infection and Immunity ◽

10.1128/iai.00956-19 ◽

2020 ◽

Vol 88 (5) ◽

Cited By ~ 2

Author(s):

Ashley L. Marcinkiewicz ◽

Ilva Lieknina ◽

Xiuli Yang ◽

Patricia L. Lederman ◽

Thomas M. Hart ◽

...

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Binding Site ◽

Causative Agent ◽

Vaccine Candidate ◽

Binding Activity ◽

Factor H ◽

Tick Feeding ◽

Content Type ◽

Complement Regulator

ABSTRACT The spirochete Borrelia burgdorferi sensu lato is the causative agent of Lyme disease (LD). The spirochetes produce the CspZ protein that binds to a complement regulator, factor H (FH). Such binding downregulates activation of host complement to facilitate spirochete evasion of complement killing. However, vaccination with CspZ does not protect against LD infection. In this study, we demonstrated that immunization with CspZ-YA, a CspZ mutant protein with no FH-binding activity, protected mice from infection by several spirochete genotypes introduced via tick feeding. We found that the sera from CspZ-YA-vaccinated mice more efficiently eliminated spirochetes and blocked CspZ FH-binding activity than sera from CspZ-immunized mice. We also found that vaccination with CspZ, but not CspZ-YA, triggered the production of anti-FH antibodies, justifying CspZ-YA as an LD vaccine candidate. The mechanistic and efficacy information derived from this study provides insights into the development of a CspZ-based LD vaccine.

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Critical Role for Interleukin-25 in Host Protective Th2 Memory Response against Heligmosomoides polygyrus bakeri

Infection and Immunity ◽

10.1128/iai.00180-16 ◽

2016 ◽

Vol 84 (12) ◽

pp. 3328-3337 ◽

Cited By ~ 13

Author(s):

Chenlin Pei ◽

Chao Zhao ◽

An-Jiang Wang ◽

Anya X. Fan ◽

Viktoriya Grinchuk ◽

...

Keyword(s):

Smooth Muscle ◽

Critical Role ◽

Nematode Infection ◽

Intestinal Smooth Muscle ◽

Heligmosomoides Polygyrus ◽

Content Type ◽

Memory Response ◽

Worm Expulsion ◽

Interleukin 25

Infection with parasitic nematodes, especially gastrointestinal geohelminths, affects hundreds of millions of people worldwide and thus poses a major risk to global health. The host mechanism of defense against enteric nematode infection remains to be fully understood, but it involves a polarized type 2 immunity leading to alterations in intestinal function that facilitate worm expulsion. We investigated the role of interleukin-25 (IL-25) in host protection against Heligmosomoides polygyrus bakeri infection in mice. Our results showed that Il25 and its receptor subunit, Il17rb , were upregulated during a primary infection and a secondary challenge infection with H. polygyrus bakeri . Genetic deletion of IL-25 (IL-25 −/− ) led to an attenuated type 2 cytokine response and increased worm fecundity in mice with a primary H. polygyrus bakeri infection. In addition, the full spectrum of the host memory response against a secondary infection with H. polygyrus bakeri was severely impaired in IL-25 −/− mice, including delayed type 2 cytokine responses, an attenuated functional response of the intestinal smooth muscle and epithelium, diminished intestinal smooth muscle hypertrophy/hyperplasia, and impaired worm expulsion. Furthermore, exogenous administration of IL-25 restored the host protective memory response against H. polygyrus bakeri infection in IL-25 −/− mice. These data demonstrate that IL-25 is critical for host protective immunity against H. polygyrus bakeri infection, highlighting its potential application as a therapeutic agent against parasitic nematode infection worldwide.

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Reservoir Competence of Various Rodents for the Lyme Disease Spirochete Borrelia spielmanii

Applied and Environmental Microbiology ◽

10.1128/aem.00022-11 ◽

2011 ◽

Vol 77 (11) ◽

pp. 3565-3570 ◽

Cited By ~ 37

Author(s):

Dania Richter ◽

Daniela B. Schlee ◽

Franz-Rainer Matuschka

Keyword(s):

Lyme Disease ◽

Rodent Species ◽

Content Type ◽

Edible Dormouse ◽

Reservoir Hosts ◽

Norway Rats

ABSTRACTTo determine whether the pathogenic Lyme disease spirocheteBorrelia spielmaniiis adapted exclusively to garden dormice, we compared the reservoir competence of various rodent species for this spirochete, including sympatric and peridomestic rodents. The different kinds of rodents varied in their attractiveness to nymphal ticks and their level of susceptibility to tick-borneB. spielmaniiinfection, but only the edible dormouse appeared to be refractory. Although hazel dormice and Norway rats became infectious to ticks somewhat later than did garden dormice, they remained infectious for a longer period of time. During the course of a tick season, garden and hazel dormice contributed theoretically more than twice as manyB. spielmanii-infected ticks than the somewhat less susceptible Norway rats and wood or yellow-necked mice. Hazel dormice appeared to be extraordinarily competent as reservoir hosts forB. spielmanii. Because peridomestic rodents proved to be reservoir competent, urban foci of transmission ofB. spielmaniimay affect the health of townspeople.

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Oral Bacterial Communities in Individuals with Type 2 Diabetes Who Live in Southern Thailand

Applied and Environmental Microbiology ◽

10.1128/aem.02821-13 ◽

2013 ◽

Vol 80 (2) ◽

pp. 662-671 ◽

Cited By ~ 18

Author(s):

Kanokporn Kampoo ◽

Rawee Teanpaisan ◽

Ruth G. Ledder ◽

Andrew J. McBain

Keyword(s):

Type 2 Diabetes ◽

Dental Caries ◽

Bacterial Communities ◽

Glycosylated Hemoglobin ◽

Content Type ◽

Supragingival Plaque ◽

Southern Thailand ◽

Acid Tolerant ◽

Dna Profiles

ABSTRACTType 2 diabetes mellitus is increasingly common in Thailand and elsewhere. In the present investigation, the bacteriological composition of saliva and supragingival plaque in Thai diabetics with and without active dental caries and in nondiabetics was determined by differential culture and eubacterial DNA profiling. Potential associations between fasting blood sugar and glycosylated hemoglobin (biomarkers of current and historical glucose control, respectively) with decayed, missing, and filled teeth and with salivaryStreptococcusandLactobacilluscounts were also investigated. The incidence of active dental caries was greater in the Thai diabetics than in nondiabetics, and the numbers of total streptococci and lactobacilli were significantly higher in supragingival plaque from diabetics than in nondiabetics.Lactobacilluscounts in the saliva and supragingival plaque of diabetics with active caries were significantly higher than those in diabetics without active caries. Oral eubacterial DNA profiles of diabetic versus nondiabetic individuals and of diabetics with active caries versus those without active caries could not be readily differentiated through cluster analysis or multidimensional scaling. The elevated caries incidence in the Thai diabetics was positively associated with numbers of bacteria of the acidogenic/acid-tolerant generaStreptococcusandLactobacillus. Lactobacillusbacterial numbers were further elevated in diabetics with active caries, although salivary eubacterial DNA profiles were not significantly altered.

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Complete Genome Sequences of Six Novel Macaca mulatta Papillomavirus Types Isolated from Genital Sites of Rhesus Monkeys in Hong Kong SAR, China

Microbiology Resource Announcements ◽

10.1128/mra.01414-18 ◽

2018 ◽

Vol 7 (22) ◽

Cited By ~ 1

Author(s):

Teng Long ◽

Po Yee Wong ◽

Wendy C. S. Ho ◽

Robert D. Burk ◽

Paul K. S. Chan ◽

...

Keyword(s):

Hong Kong ◽

Macaca Mulatta ◽

Complete Genome ◽

Rhesus Monkeys ◽

Genome Sequences ◽

Content Type ◽

Complete Genomes ◽

Hong Kong Sar

The complete genomes of six Macaca mulatta papillomavirus types isolated from genital sites of rhesus monkeys were characterized, and less than 72% identity with the complete L1 genes of known papillomaviruses was found. Macaca mulatta papillomavirus type 2 (MmPV2), MmPV3, and MmPV6 cluster into the genus Alphapapillomavirus, and MmPV4, MmPV5, and MmPV7 cluster into the genus Gammapapillomavirus.

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Red meat consumption and type 2 diabetes mellitus risk

Nutrition & Food Science ◽

10.1108/nfs-12-2014-0103 ◽

2015 ◽

Vol 45 (4) ◽

pp. 524-541

Author(s):

Emma Derbyshire ◽

Carrie Ruxton

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Clinical Studies ◽

Meat Consumption ◽

Red Meat ◽

Review Literature ◽

Processed Meat ◽

Content Type

Purpose – This review aims to evaluate and review literature published in the area of rising concerns that red meat consumption may be associated with risk of type 2 diabetes mellitus (T2DM), although there have been discrepancies between study findings, and put the findings into context. Design/methodology/approach – Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review was undertaken to locate and summarise relevant studies which included epidemiological and clinical studies published between 2004 and 2014. Findings – A total of 23 studies were found, with 21 epidemiological and two clinical studies meeting the criteria. Overall, the totality of the evidence indicates that while processed meat consumption appears to be associated with T2DM risk, the effect is much weaker for red meat, with some associations attenuated after controlling for body weight parameters. Where studies have considered high intakes in relation to T2DM risk, meat intake has tended to exceed 600 g per week. Therefore, keeping red meat intakes within recommended guidelines of no more than 500 g per week, while opting for lean cuts or trimming fat, would seem to be an evidence-based response. Research limitations/implications – The majority of studies conducted to date have been observational cohorts which cannot determine cause and effect. Most of these used food frequency questionnaires which are known to be subject to misclassification errors (Brown, 2006). Clearly, more randomised controlled trials are needed to establish whether red meat consumption impacts on markers of glucose control. Until then, conclusions can only be viewed as speculative. Originality/value – This paper provides an up-to-date systematic review of the literature, looking at inter-relationships between red meat consumption and T2DM risk.

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The Western Progression of Lyme Disease: Infectious and NonclonalBorrelia burgdorferi Sensu LatoPopulations in Grand Forks County, North Dakota

Applied and Environmental Microbiology ◽

10.1128/aem.02422-14 ◽

2014 ◽

Vol 81 (1) ◽

pp. 48-58 ◽

Cited By ~ 12

Author(s):

Brandee L. Stone ◽

Nathan M. Russart ◽

Robert A. Gaultney ◽

Angela M. Floden ◽

Jefferson A. Vaughan ◽

...

Keyword(s):

Lyme Disease ◽

16S Rrna ◽

16S Rrna Gene ◽

North Dakota ◽

Intergenic Spacer ◽

Rrna Gene ◽

Content Type ◽

Intergenic Spacer Region ◽

Grand Forks ◽

The 16S Rrna Gene

ABSTRACTScant attention has been paid to Lyme disease,Borrelia burgdorferi,Ixodes scapularis, or reservoirs in eastern North Dakota despite the fact that it borders high-risk counties in Minnesota. Recent reports ofB. burgdorferiandI. scapularisin North Dakota, however, prompted a more detailed examination. Spirochetes cultured from the hearts of five rodents trapped in Grand Forks County, ND, were identified asB. burgdorferi sensu latothrough sequence analyses of the 16S rRNA gene, the 16S rRNA gene-ileTintergenic spacer region,flaB,ospA,ospC, andp66. OspC typing revealed the presence of groups A, B, E, F, L, and I. Two rodents were concurrently carrying multiple OspC types. Multilocus sequence typing suggested the eastern North Dakota strains are most closely related to those found in neighboring regions of the upper Midwest and Canada. BALB/c mice were infected withB. burgdorferiisolate M3 (OspC group B) by needle inoculation or tick bite. Tibiotarsal joints and ear pinnae were culture positive, andB. burgdorferiM3 was detected by quantitative PCR (qPCR) in the tibiotarsal joints, hearts, and ear pinnae of infected mice. Uninfected larvalI. scapularisticks were able to acquireB. burgdorferiM3 from infected mice; M3 was maintained inI. scapularisduring the molt from larva to nymph; and further, M3 was transmitted from infectedI. scapularisnymphs to naive mice, as evidenced by cultures and qPCR analyses. These results demonstrate that isolate M3 is capable of disseminated infection by both artificial and natural routes of infection. This study confirms the presence of unique (nonclonal) and infectiousB. burgdorferipopulations in eastern North Dakota.

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First Description of Two Sequence Type 2 Acinetobacter baumannii Isolates Carrying OXA-23 Carbapenemase in Pagellus acarne Fished from the Mediterranean Sea near Bejaia, Algeria

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02384-15 ◽

2016 ◽

Vol 60 (4) ◽

pp. 2513-2515 ◽

Cited By ~ 16

Author(s):

Soumia Brahmi ◽

Abdelaziz Touati ◽

Axelle Cadière ◽

Nassima Djahmi ◽

Alix Pantel ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Mediterranean Sea ◽

Sequence Type ◽

Content Type ◽

Carbapenem Resistant ◽

Selective Agar ◽

Agar Media ◽

The Mediterranean ◽

First Time

ABSTRACTTo determine the occurrence of carbapenem-resistantAcinetobacter baumanniiin fish fished from the Mediterranean Sea near the Bejaia coast (Algeria), we studied 300 gills and gut samples that had been randomly and prospectively collected during 1 year. After screening on selective agar media, using PCR arrays and whole-genome sequencing, we identified for the first time two OXA-23-producingA. baumanniistrains belonging to the widespread sequence type 2 (ST2)/international clone II and harboring aminoglycoside-modifying enzymes [aac(6′)-Ib andaac(3′)-I genes].

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