Breakthroughs in microbiology made possible with organoids

To study the host-pathogen interactions with medical and veterinary relevance, researchers have recently applied organoid technology.Organoids revolutionized biomedical research in the last decade due to their ability to recapitulate the physiological properties of whole organs in cell culture.For the field of microbiology, organoids have allowed the study of previously recalcitrant pathogens that would only replicate in their natural host.Nowadays, a large list of viruses, bacteria, fungi, and parasites have been studied using organoids.Here, we describe breakthrough studies that have had or are predicted to have major impacts in the microbiology field, which would not have been possible without the use of organoid technology.OAU : Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly:rganoids: What are they, and what are they used for?While the two-dimensional (2D) culture of host cells has provided valuable insights for the microbiology field, they lack many of the components needed to recreate the natural host environment for investigating pathogens, such as the microbiota, cellular complexity, and polarity.Organoids are cultured from stem cells and form three-dimensional (3D) structures that mimic the organ, including multiple cell types, protein expression, and functions such as absorption, barrier function, and nutrient uptake (Fig 1).Human intestinal, lung, kidney, brain, and liver organoids have all been used to study host-microbe interactions and to test drug potential treatments.Because the brain has a particularly complex structure and strict restrictions exist for obtaining human samples, human brain organoids (HBOs) have been a significant advance for the study of microbes that infect the brain. What rapid breakthroughs occurred studying pandemic viruses?Zika virus (ZAU : PleasenotethattheabbreviationZIKVhasbeenintroducedforZikavirusinthesentenceZika IKV) spreads by the bite of an infected Aedes spp.mosquito causing mild flu symptoms in adults and congenital Zika syndrome in newborns.Congenital Zika syndrome includes several birth defects but is most known for small infant head size called microcephaly.Zika infection of HBO allowed the mechanism by which ZIKV affects the neurons to be determined [1,2] as well as the evaluation of potential treatments [3].ZIKV-infected HBOs have shown that replication of the virus killed neural precursors that led to microcephaly [1,2].The microcephaly model of ZIKV in HBO further showed thinning of the cortices and impaired cortical expansion, which also lead to HBO size reduction [4].Neurosphere and HBO infection with Brazilian and African ZIKV strains showed larger reductions in the proliferative zones, greater disruption of the cortical layers, and an increased number of apoptotic cells with the Brazilian compared to the African ZIKV strain [5].Other advantages and limitations of the HBO to study ZIKV over other in vitro models as well as advances to understand the affections in HBO that resemble microcephaly were recently summarized [6].