Mycobacterium bovis, also called M. tuberculosis var. bovis, is a bacterium belonging to the M. tuberculosis complex (i.e., MTBC) and which can cause through zoonotic transmission another form of human tuberculosis (Tb). It is above all the agent of bovine tuberculosis (i.e., bTb) which affects not only cattle (wild or farmed) but also a large diversity of other wild mammals worldwide. An increasing number of infected animal cases are being discovered in many regions of the world, thus raising the problem of tuberculosis transmission, including to humans, more complex than previously thought. Efforts have been made in terms of vaccination or culling of populations of host carrier species, such as the badger for example, however leading to consequences of greater dispersion of the infectious agent. M. bovis shows a more or less significant capacity to persist outside its hosts, particularly in the environment under certain abiotic and biotic conditions. This bacillus can be transmitted and spread in many ways, including through aerosol, mucus and sputum, urine and feces, by direct contact with infected animals, their dead bodies or rather via their excreta or by inhalation of aerosols, depending on the host species concerned.

In this paper, Calenge and his collaborators (Callenge et al. 2024) benefited from a national surveillance program on M. bovis cases in wild species, set up in 2011 in France, i.e., Sylvatub, for detecting and monitoring M. bovis infection in European badger (Meles meles) populations. Sylvatub is a participatory program involving both national and local stakeholder systems in order to determine changes in bTb infection levels in domestic and wild animal species. This original work had two aims: to describe spatial disease dynamics in the three clusters under scrutiny using a complex Bayesian model; and to develop indicators for the monitoring of the M. bovis infection by stakeholders and decision-makers of the program. This paper is timely and very comprehensive.

In this cogent study, the authors illustrate this point by using epidemiological surveillance to obtain large amounts of data (which is generally lacking in human epidemiology, but more dramatically lacking in animal epidemiology) and a highly sophisticated biostatistical analysis (Callenge et al. 2024). It is in itself a demonstration of the current capabilities of population dynamics applied to infectious disease situations, in this case animal, in the rapidly developing discipline of disease ecology and evolution. One of the aims of the study is to propose statistical models that can be used by the different stakeholders in charge, for instance, of wildlife conservation or the regional or State veterinary services to assess disease risk in the most affected regions.

References

Assel AKHMETOVA​, Jimena GUERRERO​, Paul McADAM, Liliana CM SALVADOR​, Joseph CRISPELL​, John LAVERY​, Eleanor PRESHO​, Rowland R KAO​, Roman BIEK​, Fraser MENZIES​, Nigel TRIMBLE​, Roland HARWOOD​, P Theo PEPLER, Katarina ORAVCOVA​, Jordon GRAHAM​, Robin SKUCE​, Louis DU PLESSIS​, Suzan THOMPSON​, Lorraine WRIGHT​, Andrew W BYRNE​, Adrian R ALLEN. 2023. Genomic epidemiology of Mycobacterium bovis infection in sympatric badger and cattle populations in Northern Ireland. Microbial Genomics 9: mgen001023. https://doi.org/10.1099/mgen.0.001023

Roman BIEK, Anthony O’HARE, David WRIGHT, Tom MALLON, Carl McCORMICK, Richard J ORTON, Stanley McDOWELL, Hannah TREWBY, Robin A SKUCE, Rowland R KAO. 2012. Whole genome sequencing reveals local transmission patterns of Mycobacterium bovis in sympatric cattle and badger populations. PLoS Pathogens 8: e1003008. https://doi.org/10.1371/journal.ppat.1003008

Clément CALENGE, Ariane PAYNE, Edouard REVEILLAUD, Céline RICHOMME, Sébastien GIRARD, Stephanie DESVAUX. 2024. Assessing the dynamics of Mycobacterium bovis infection in three French badger populations. bioRxiv, ver. 3 peer-reviewed and recommended by Peer Community In Infections. https://doi.org/10.1101/2023.05.31.543041

Marc CHOISY, Pejman ROHANI. 2006. Harvesting can increase severity of wildlife disease epidemics. Proceedings of the Royal Society, London, Ser. B 273: 2025-2034. https://doi.org/10.1098/rspb.2006.3554

Shannon C DUFFY, Sreenidhi SRINIVASAN, Megan A SCHILLING, Tod STUBER, Sarah N DANCHUK, Joy S MICHAEL, Manigandan VENKATESAN, Nitish BANSAL, Sushila MAAN, Naresh JINDAL, Deepika CHAUDHARY, Premanshu DANDAPAT, Robab KATANI, Shubhada CHOTHE, Maroudam VEERASAMI, Suelee ROBBE-AUSTERMAN, Nicholas JULEFF, Vivek KAPUR, Marcel A BEHR. 2020. Reconsidering Mycobacterium bovis as a proxy for zoonotic tuberculosis: a molecular epidemiological surveillance study. Lancet Microbe 1: e66-e73. https://doi.org/10.1016/S2666-5247(20)30038-0

Jean-François GUEGAN. 2019. The nature of ecology of infectious disease. The Lancet Infectious Diseases 19. https://doi.org/10.1016/s1473-3099(19)30529-8

Brandon H HAYES, Timothée VERGNE, Mathieu ANDRAUD, Nicolas ROSE. 2023. Mathematical modeling at the livestock-wildlife interface: scoping review of drivers of disease transmission between species. Frontiers in Veterinary Science 10: 1225446. https://doi.org/10.3389/fvets.2023.1225446

David KING, Tim ROPER, Douglas YOUNG, Mark EJ WOOLHOUSE, Dan COLLINS, Paul WOOD. 2007. Bovine tuberculosis in cattle and badgers. Report to Secretary of State about tuberculosis in cattle and badgers. London, UK. https://www.bovinetb.info/docs/RBCT_david_%20king_report.pdf  

Robert MM SMITH , Francis DROBNIEWSKI, Andrea GIBSON, John DE MONTAGUE, Margaret N LOGAN, David HUNT, Glyn HEWINSON, Roland L SALMON, Brian O’NEILL. 2004. Mycobacterium bovis Infection, United Kingdom. Emerging Infectious Diseases 10: 539-541. https://doi.org/10.3201/eid1003.020819 

​​Diptera-borne pathogens rank among the most serious health threats to vertebrate organisms around the world, particularly in tropical areas undergoing strong human impacts – e.g., urbanization and farming –, where social unrest and poor economies exacerbate the risk (Allen et al. 2017; Robles-Fernández et al. 2022). Although scientists have acquired a detailed knowledge on the life-history of malaria parasites (Pacheco and Escalante 2023), they still do not have enough information about their insect vectors to make informed management and preventive decisions (Santiago-Alarcon 2022).

In this sense, I am pleased to recommend the study of Vantaux et al. (2023), where authors conducted an experimental and theoretical study to analyzed how the diversity of blood sources (i.e., human, cattle, sheep, and chicken) affected the fitness of the human malaria parasite – Plasmodium falciparum – and its mosquito vector – Anopheles gambiae s.l.

The study was conducted in Burkina Faso, West Africa. Interestingly, authors did not find a significant effect of blood meal source on parasite development, and a seemingly low impact on the fitness of mosquitoes that were exposed to parasites. However, mosquitoes’ feeding rate, survival, fecundity, and offspring size were negatively affected by the type of blood meal ingested. In general, chicken blood represented the worst meal source for the different measures of mosquito fitness, and sheep blood seems to be the least harmful. This result was supported by the theoretical model, where vectorial capacity was always better when mosquitoes fed on sheep blood compared to cow and chicken blood. Thus, the knowledge generated by this study provides a pathway to reduce human infection risk by managing the diversity of farm animals. For instance, transmission to humans can decrease when chickens and cows represent most of the available blood sources in a village.

These results along with other interesting details of this study, represent a clear example of the knowledge and understanding of insect vectors that we need to produce in the future, particularly to manage and prevent hazards and risks (sensu Hoseini et al. 2017).

REFERENCES

Allen T., et al., Global hotspots and correlates of emerging zoonotic diseases. Nat. Commun. 8, 1124. (2017). https://doi.org/10.1038/s41467-017-00923-8

Hosseini P.R., et al., Does the impact of biodiversity differ between emerging and endemic pathogens? The need to separate the concepts of hazard and risk. Philos. Trans. R. Soc. Lond. B Biol. Sci. 372, 20160129 (2017). https://doi.org/10.1098/rstb.2016.0129

Pacheco M.A., and Escalante, A.A., Origin and diversity of malaria parasites and other Haemosporida. Trend. Parasitol. (2023) https://doi.org/10.1016/j.pt.2023.04.004

Robles-Fernández A., et al., Wildlife susceptibility to infectious diseases at global scales. PNAS 119: e2122851119. (2022). https://doi.org/10.1073/pnas.2122851119

Santiago-Alarcon D. A meta-analytic approach to investigate mosquitoes’ (Diptera: Culicidae) blood feeding preferences from non-urban to urban environments. In: Ecology and Control of Vector-borne Diseases, vol. 7 (R.G. Gutiérrez-López, J.G. Logan, Martínez-de la Puente J., Eds). Pp. 161-177. Wageningen Academic Publishers. eISBN: 978-90-8686-931-2 | ISBN: 978-90-8686-379-2 (2022).

Vantaux A. et al. Multiple hosts, multiple impacts: the role of vertebrate host diversity in shaping mosquito life history and pathogen transmission. bioRxiv, ver. 3 peer-reviewed and recommended by Peer Community in Infections (2023). https://doi.org/10.1101/2023.02.10.527988

Structural variations (SVs) play a key role in viral evolution, and therefore they are also important for infection dynamics. However, the contribution of structural variations to the evolution of double-stranded viruses is limited. This knowledge can help to understand the population dynamics and might be crucial for the future development of viral attenuated vaccines.

In this study, Fuandila et al (1) use the Cyprinid herpesvirus 3 (CyHV-3), commonly known as koi herpesvirus (KHV), to investigate the variability and contribution of structural variations (SV) for viral evolution after 99 passages in vitro. This virus, with the largest genome among herperviruses, causes a lethal infection in common carp and koi associated with mortalities up to 95% (2). Interestingly, KHV infections are caused by haplotype mixtures, which possibly are a source of genome diversification, but make genomic comparisons more difficult.

The authors have used ultra-deep long-read sequencing of two passages, P78 and P99, which were previously described to have differences in virulence. They have found a surprisingly high and wide distribution of SVs along the genome, which were enriched in inversion and deletion events and that often led to defective viral genomes. Although it is known that these defective viral genomes negatively impact viral replication, their implications for virus persistence are still unclear.

Subsequently, the authors concentrated on the virulence-relevant region ORF150, which was found to be different in P78 (deletion in 100% of the reads) and P99 (reference-like haplotype). To understand this loss and gain of full ORF150, they searched for SV turn-over in 10 intermediate passages. This analysis revealed that by passage 10 deleted and inverted (attenuated) haplotypes had already appeared, steadily increased frequency until P78, and then completely disappeared between P78 and P99. This is a striking result that raises new questions as to how this clearance occurs, which is really important as these reversions may result in undesirable increases in virulence of live-attenuated vaccines.

We recommend this preprint because its use of ultra-deep long-read sequencing has permitted to better understand the role of SV diversity and dynamics in viral evolution. This study shows an unexpectedly high number of structural variations, revealing a novel source of virus diversification and confirming the different mixtures of haplotypes in different passages, including the gain of function. This research provides basic knowledge for the future design of live-attenuated vaccines, to prevent the reversion to virulent viruses. 

References

(1)  Fuandila NN, Gosselin-Grenet A-S, Tilak M-K, Bergmann SM, Escoubas J-M, Klafack S, Lusiastuti AM, Yuhana M, Fiston-Lavier A-S, Avarre J-C, Cherif E (2022) Structural variation turnovers and defective genomes: key drivers for the in vitro evolution of the large double-stranded DNA koi herpesvirus (KHV). bioRxiv, 2022.03.10.483410, ver. 4 peer-reviewed and recommended by Peer Community in Infections. https://doi.org/10.1101/2022.03.10.483410

(2)  Sunarto A, McColl KA, Crane MStJ, Sumiati T, Hyatt AD, Barnes AC, Walker PJ. Isolation and characterization of koi herpesvirus (KHV) from Indonesia: identification of a new genetic lineage. Journal of Fish Diseases, 34, 87-101. https://doi.org/10.1111/j.1365-2761.2010.01216.x 

The impact of virus infection of a plant on an aphid’s behaviour has been observed in many studies [1]. Indeed, virus infection can alter plant biochemistry through the emission of volatile organic compounds and plant tissue content modification. These alterations can further impact the interactions between plants and aphids. However, although it is a well-known phenomenon, very few studies have explored the consequences of plant virus infection on the gene expression of aphids to understand better the aphid’s manipulation by the plant virus. In this context, the recommended study [2] reports a comprehensive transcriptomic analysis of the genes expressed by one aphid species, Myzus persicae, a vector of several plant viruses, when feeding on plants. Michelle Heck underlined how significant this study is for comprehending the molecular bases of aphid-vector manipulation by plant viruses (see below).

Interestingly, the study design has integrated several factors that might influence the gene expression of M. persicae when feeding on the plant. Indeed, the authors investigated the effect of two plant species (Arabidopsis thaliana and Camelia sativa) and two virus species [turnip yellows virus (TuYV) and cauliflower mosaic virus (CaMV)]. Noteworthy, the transmission mode of TuYV is circulative and persistent, while CaMV is transmitted by a semi-persistent non-circulative mode. As Juan José Lopez Moya mentioned, multiple comparisons allowed the identification of the different responses of aphids in front of different host plants infected or not by different viruses (see below). This publication is complementary to a previous publication from the same team focusing on plant transcriptome analysis [3].

Thanks to their experimental design, the authors identified genes commonly deregulated by both viruses and/or both plant species and deregulated genes by a single virus or a single plant. Figure 4 nicely summarizes the number of deregulated genes. A thorough discussion on the putative role of deregulated genes in different conditions gave a comprehensive follow-up of the results and their impact on the current knowledge of plant-virus-vector interactions.

This study has now opened the gate to promising research focusing on the functional validation of the identified genes while also narrowing the study from the body to the tissue level.

References:

1. Carr JP, Tungadi T, Donnelly R, Bravo-Cazar A, Rhee S-J, Watt LG, Mutuku JM, Wamonje FO, Murphy AM, Arinaitwe W, Pate AE, Cunniffe NJ, Gilligan CA (2020) Modelling and manipulation of aphid-mediated spread of non-persistently transmitted viruses. Virus Research, 277, 197845. https://doi.org/10.1016/j.virusres.2019.197845

2. Chesnais Q, Golyaev V, Velt A, Rustenholz C, Verdier M, Brault V, Pooggin MM, Drucker M (2022) Transcriptome responses of the aphid vector Myzus persicae are shaped by identities of the host plant and the virus. bioRxiv , 2022.07.18.500449, ver. 5 peer-reviewed and recommended by Peer Community in Infections. https://doi.org/10.1101/2022.07.18.500449

3. Chesnais Q, Golyaev V, Velt A, Rustenholz C, Brault V, Pooggin MM, Drucker M (2022) Comparative Plant Transcriptome Profiling of Arabidopsis thaliana Col-0 and Camelina sativa var. Celine Infested with Myzus persicae Aphids Acquiring Circulative and Noncirculative Viruses Reveals Virus- and Plant-Specific Alterations Relevant to Aphid Feeding Behavior and Transmission. Microbiology Spectrum, 10, e00136-22. https://doi.org/10.1128/spectrum.00136-22

Ticks are amongst the most important pathogen vectors in medical and veterinary clinical settings worldwide (Dantas-Torres et al., 2012). Like other holobionts, ticks live in association with a diverse microbiota. It includes tick-borne pathogens (TBP) and other microorganisms that have a beneficial or detrimental effect on the physiology of the host and can also affect the transmission of TBP to animals or humans. In this microbiota, primary endosymbionts, which are obligatory and inheritable, play a role in tick reproduction, the host defense and adaptation to varying environmental conditions (Duron et al., 2018). However, the effect of the microbiota structure and of the endosymbionts on tick fitness and reproduction is not well known. The soft tick Ornithodoros moubata, a parasite known to transmit African swine fever virus (Vial, 2009), is known to host Francisella-like and Rickettsia endosymbionts (Duron et al., 2018). These endosymbionts carry genes involved in B vitamin synthesis which may be supplemented to the host (Bonnet & Pollet, 2021). 

Here, the authors investigated the role of endosymbionts on the reproductive fitness of Ornithodoros moubata by conducting two experiments (Taraveau et al., 2023). First, they tested the effect of antibiotic treatment of 366 first-stage nymphs on the main endosymbionts Francisella-like and Rickettsia, and measured the endosymbionts presence overtime by qPCR. Second, they surveyed the effect of antibiotic treatment with or without the addition of B vitamins on the survival and reproductive fitness of 132 females over 50 days. This second experiment intended to identify whether the endosymbionts have an effect on the host reproduction or on its nutrition. The supplementation of B vitamin did not have a drastic effect on tick fitness or reproductive traits. However, antibiotic treatments reduced the presence of endosymbionts while increasing tick survival, suggesting a potential cost of hosting endosymbionts on the tick fitness.

The authors did a lot of work to thoroughly follow the propositions from Dr Raggi, Dr Aivelo and myself to reconstruct and to revise the manuscript. I believe that the manuscript now reads very well and the answers to the reviews also add some value to the manuscript. As Dr Aivelo pointed out, “this study follows the traditional path of so-called population perturbation studies, where ecologists have administered antibiotics or antihelminths to different animals and seen how the community changes and what effects this has on the host fitness and survival”. As both reviewers stated, results from this study are valuable and provide important basic knowledge that will likely help conduct future experiments on tick microbiota. This recommendation is the result of the thorough reviewing work of Dr Aivelo and Dr Raggi which I warmly thank.
 
References

Bonnet, S. I., & Pollet, T. (2021). Update on the intricate tango between tick microbiomes and tick‐borne pathogens. Parasite Immunology, 43(5), e12813. https://doi.org/10.1111/pim.12813

Dantas-Torres, F., Chomel, B. B., & Otranto, D. (2012). Ticks and tick-borne diseases: A One Health perspective. Trends in Parasitology, 28(10), 437–446. https://doi.org/10.1016/j.pt.2012.07.003

Duron, O., Morel, O., Noël, V., Buysse, M., Binetruy, F., Lancelot, R., Loire, E., Ménard, C., Bouchez, O., Vavre, F., & Vial, L. (2018). Tick-Bacteria Mutualism Depends on B Vitamin Synthesis Pathways. Current Biology, 28(12), 1896-1902.e5. https://doi.org/10.1016/j.cub.2018.04.038

Taraveau, F., Pollet, T., Duhayon, M., Gardès, L., & Jourdan-Pineau, H. (2023). Influence of endosymbionts on the reproductive fitness of the tick Ornithodoros moubata. bioRxiv, ver.3, peer-reviewed and recommended by Peer Community in Infections. https://doi.org/10.1101/2023.05.09.539061

Vial, L. (2009). Biological and ecological characteristics of soft ticks (Ixodida: Argasidae) and their impact for predicting tick and associated disease distribution. Parasite, 16(3), 191–202. https://doi.org/10.1051/parasite/2009163191