Prevalence and implications of multiple-strain infections

Balmer, Oliver; Tanner, Marcel

doi:10.1016/s1473-3099(11)70241-9

Cited by 217 publications

(234 citation statements)

References 147 publications

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“…Which of these mechanisms is most important in the case of B. afzelii? Interference competition occurs in some bacteria, including Escherichia coli and Haemophilus influenzae [1], but has, as far as we are aware, not been described in Borrelia. Antibody responses to OspC are largely strain-specific, but responses to other outer surface proteins (e.g.…”

Section: Discussionmentioning

confidence: 92%

Within-host competition betweenBorrelia afzelii ospCstrains in wild hosts as revealed by massively parallel amplicon sequencing

Strandh

Råberg

2015

Phil. Trans. R. Soc. B

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Infections frequently consist of more than one strain of a given pathogen. Experiments have shown that co-infecting strains often compete, so that the infection intensity of each strain in mixed infections is lower than in single strain infections. Such within-host competition can have important epidemiological and evolutionary consequences. However, the extent of competition has rarely been investigated in wild, naturally infected hosts, where there is noise in the form of varying inoculation doses, asynchronous infections and host heterogeneity, which can potentially alleviate or eliminate competition. Here, we investigated the extent of competition between Borrelia afzelii strains (as determined by ospC genotype) in three host species sampled in the wild. For this purpose, we developed a protocol for 454 amplicon sequencing of ospC , which allows both detection and quantification of each individual strain in an infection. Each host individual was infected with one to six ospC strains. The infection intensity of each strain was lower in mixed infections than in single ones, showing that there was competition. Rank-abundance plots revealed that there was typically one dominant strain, but that the evenness of the relative infection intensity of the different strains in an infection increased with the multiplicity of infection. We conclude that within-host competition can play an important role under natural conditions despite many potential sources of noise, and that quantification by next-generation amplicon sequencing offers new possibilities to dissect within-host interactions in naturally infected hosts.

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Section: Discussionmentioning

confidence: 92%

Within-host competition betweenBorrelia afzelii ospCstrains in wild hosts as revealed by massively parallel amplicon sequencing

Strandh

Råberg

2015

Phil. Trans. R. Soc. B

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“…enetically diverse pathogens often establish mixed infections in their hosts that consist of multiple strains or genotypes of the same pathogen species (1)(2)(3). Mixed infections represent a major problem for public health because they complicate the development of treatments and vaccines (1,4).…”

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confidence: 99%

“…Mixed infections represent a major problem for public health because they complicate the development of treatments and vaccines (1,4). Some pathogen strains are more infectious or do more harm to certain host species (5,6).…”

mentioning

confidence: 99%

Multistrain Infections with Lyme Borreliosis Pathogens in the Tick Vector

Durand

Herrmann

Genné

et al. 2017

Appl Environ Microbiol

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Mixed or multiple-strain infections are common in vector-borne diseases and have important implications for the epidemiology of these pathogens. Previous studies have mainly focused on interactions between pathogen strains in the vertebrate host, but little is known about what happens in the arthropod vector. Borrelia afzelii and Borrelia garinii are two species of spirochete bacteria that cause Lyme borreliosis in Europe and that share a tick vector, Ixodes ricinus. Each of these two tick-borne pathogens consists of multiple strains that are often differentiated using the highly polymorphic ospC gene. For each Borrelia species, we studied the frequencies and abundances of the ospC strains in a wild population of I. ricinus ticks that had been sampled from the same field site over a period of 3 years. We used quantitative PCR (qPCR) and 454 sequencing to estimate the spirochete load and the strain diversity within each tick. For B. afzelii, there was a negative relationship between the two most common ospC strains, suggesting the presence of competitive interactions in the vertebrate host and possibly the tick vector. The flat relationship between total spirochete abundance and strain richness in the nymphal tick indicates that the mean abundance per strain decreases as the number of strains in the tick increases. Strains with the highest spirochete load in the nymphal tick were the most common strains in the tick population. The spirochete abundance in the nymphal tick appears to be an important life history trait that explains why some strains are more common than others in nature.IMPORTANCE Lyme borreliosis is the most common vector-borne disease in the Northern Hemisphere and is caused by spirochete bacteria that belong to the Borrelia burgdorferi sensu lato species complex. These tick-borne pathogens are transmitted among vertebrate hosts by hard ticks of the genus Ixodes. Each Borrelia species can be further subdivided into genetically distinct strains. Multiple-strain infections are common in both the vertebrate host and the tick vector and can result in competitive interactions. To date, few studies on multiple-strain vector-borne pathogens have investigated patterns of cooccurrence and abundance in the arthropod vector. We demonstrate that the abundance of a given strain in the tick vector is negatively affected by the presence of coinfecting strains. In addition, our study suggests that the spirochete abundance in the tick is an important life history trait that can explain why some strains are more common in nature than others.

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“…Viral mutational robustness allows for antigenic drift, where escape mutations within targeted epitopes result in progeny with increased resistance to neutralizing mAbs or small molecules (37). Furthermore, coinfections with two or more viral strains allow for antigenic shift through gene transfer, establishing novel pathogens and complicating vaccine and treatment strategies (38)(39)(40). These continuous modes of viral evolution necessitate the development of new treatment options, which include the discovery of antiviral mAbs.…”

Section: Antiviral Mabs Discovered By Phage Displaymentioning

confidence: 99%

Phage and Yeast Display

Sheehan

Marasco

2015

Microbiol Spectr

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Despite the availability of antimicrobial drugs, the continued development of microbial resistance-established through escape mutations and the emergence of resistant strains-limits their clinical utility. The discovery of novel, therapeutic, monoclonal antibodies (mAbs) offers viable clinical alternatives in the treatment and prophylaxis of infectious diseases. Human mAb-based therapies are typically nontoxic in patients and demonstrate high specificity for the intended microbial target. This specificity prevents negative impacts on the patient microbiome and avoids driving the resistance of nontarget species. The in vitro selection of human antibody fragment libraries displayed on phage or yeast surfaces represents a group of well-established technologies capable of generating human mAbs. The advantage of these forms of microbial display is the large repertoire of human antibody fragments present during a single selection campaign. Furthermore, the in vitro selection environments of microbial surface display allow for the rapid isolation of antibodies-and their encoding genes-against infectious pathogens and their toxins that are impractical within in vivo systems, such as murine hybridomas. This article focuses on the technologies of phage display and yeast display, as these strategies relate to the discovery of human mAbs for the treatment and vaccine development of infectious diseases.

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Prevalence and implications of multiple-strain infections

Cited by 217 publications

References 147 publications

Within-host competition betweenBorrelia afzelii ospCstrains in wild hosts as revealed by massively parallel amplicon sequencing

Within-host competition betweenBorrelia afzelii ospCstrains in wild hosts as revealed by massively parallel amplicon sequencing

Multistrain Infections with Lyme Borreliosis Pathogens in the Tick Vector

Phage and Yeast Display

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