Viral strategies to lyse host microbes can sometimes involve just a single gene, although the mechanism of action can be hard to discern. In Science, Orta et al. present structures of a protein complex in which protein E of bacteriophage φX174 functions to inhibit host peptidoglycan synthesis, thereby inducing lysis.

Interferons (IFNs) and interferon-stimulated genes (ISGs) are the major players in the host innate immunity against viral infection. In a recent Nature paper, Xu et al. identified phospholipid scramblase 1 (PLSCR1) as a novel ISG that restricts severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by blocking virus-cell fusion.

Symbiotic microorganisms modulate systemic immunity with unclear mechanisms. In this issue of Cell Host & Microbe, Clarke and colleagues uncover a coherent mechanism where the systemic spread of Firmicutes cell wall glycoconjugates enhances global immune fitness while simultaneously being delicately controlled to prevent systemic inflammation.

In this issue of Cell Host & Microbe, Jang et al. decode an intriguing paradox: excessive antimicrobial peptide-regenerating family member 3 (REG3) expression in inflammatory bowel disease (IBD) patients depletes protective enterococci. This depletion impairs the NOD2 anti-inflammatory pathway and perpetuates inflammation, thus providing insight into IBD pathogenesis.

T cell responses are important for the control of acute HIV infection but become progressively dysfunctional. In this issue of Cell Host & Microbe, Dubé et al. and Takata et al. provide insights into their ongoing interplay with persistent HIV reservoirs, with implications for harnessing functional, durable responses to eliminate HIV.

Genes and regulatory mechanisms governing malaria parasite transmission and development in mosquitoes are incompletely understood. Recently, Russell and colleagues identified genes required for parasite sexual development. In this issue of Cell Host & Microbe, Ukegbu and colleagues report a genetic approach to study genes enabling parasite survival in mosquito stages.

Two recent papers published in Cell highlight the power of both top-down and bottom-up approaches to understanding the gut microbiome. The first uses ultra-deep sequencing to identify patterns across a gradient of human industrialization, while the second uses synthetic communities to determine how strain interactions impact microbiome structure and function.

In this issue of Cell Host & Microbe, Maasch et al. built a deep-learning model for proteolytic site prediction and applied this approach to modern and extinct human proteomes, revealing antimicrobial peptides. The de-extinction of archaic encrypted peptides provides a revolutionary approach for discovering functional peptides with therapeutic potential.

From corals to mammals, mucus is a conserved feature that prevents microbes from accessing the surfaces that produce it. However, interactions between mucus and microbes remain poorly understood. In this issue of Cell Host & Microbe, Smith et al. unveil that mucus binding by bacteria is crucial for host-microbe symbiosis.

Anti-cancer therapies are usually intertwined with prolonged use of drugs, which may lead to different clinical outcomes. Recently in Cell and Cell Host & Microbe, Nguyen et al. and Vallet et al., respectively, deconvolute the drug effects on gut microbiome dynamics underpinning clinical outcomes after allogeneic hematopoietic stem cell transplantation.

A recent study in Nature introduced an innovative ingestible device capable of collecting in situ samples from different regions of the human intestine for multi-omics analysis. This groundbreaking technology enables non-invasive and longitudinal characterization of the gut microbiome and associated metabolites.

New classes of antibiotics are desperately needed in our fight against antibiotic-resistant bacterial infections. Jia et al. publish a new “multi-armed” antibiotic scaffold that effectively treats methicillin-resistant Staphylococcus aureus infections in mice. These compounds are structurally unlike pre-clinical or approved antibiotics, and they may hit an “irresistible” target.

The composition of the human gut microbiome is heterogeneous across people. However, if you squint, co-abundant microbial genera emerge, accounting for much of this ecological variability. In this issue of Cell Host & Microbe, Frioux et al. provide a workflow for identifying these bacterial guilds, or “enterosignatures.”

Constitutive IFN-λ expression in the placenta protects the fetus from vertically transmitted viruses, but regulatory mechanisms are unknown. In this issue of Cell Host & Microbe, Wickramage, VanWye et al. demonstrate that Alu RNAs within a microRNA cluster important for placental development mimic viral molecular patterns to mediate protection.

The contribution of the gut microbiome to immune responsiveness is largely unknown. In a recent Nature Medicine article, Stein-Thoeringer et al. assess the microbiome configuration before cancer immunotherapy and determine the impact of antibiotic-masked microbial features on therapy’s effectiveness. This provides a framework for identifying microbial signatures to inform clinical strategies.

Cesarean section rates continue to rise globally, and C-sectioned infants are at a higher risk of adverse child outcomes. In this issue of Cell Host & Microbe, Zhou et al. report that vaginal microbial transfer (VMT) from birth mother to infant post-delivery may alter infant gut microbiota and improve neurodevelopment.

The colon mucus layer is organized with an inner colon mucus layer that is impenetrable to bacteria and an outer mucus layer that is expanded to allow microbiota colonization. A major component of mucus is MUC2, a glycoprotein that is extensively decorated, especially with O-glycans. In the intestine, goblet cells are specialized in controlling glycosylation and making mucus. Some microbiota members

COVID-19 highlighted inequitable vaccine distribution and the urgent need for vaccine manufacturing capacity on the African continent. This resulted in a burst of scientific engagement and international funding to augment capacity on the continent. However, short-term investment needs to be reinforced by a robust, strategic long-term plan to ensure sustainability.

The scientific community improvised to respond quickly to the SARS-CoV-2 pandemic without a template on how to work together on a global scale to understand and combat the virus. Here, we describe how we tackled impediments to success and the valuable lessons learned that prepare us for a future pandemic.

Pregnant women are at high risk of adverse outcomes in the setting of viral-associated outbreaks and pandemics. In this forum, we discuss the impact of past and current pandemics on pregnant women and make recommendations to protect this vulnerable population.

The coronavirus disease has swept the world, bringing scientists from multiple disciplines together to work on a focused cause. In this forum, we discuss different roles that microbiota, malnutrition, and immunity have on severity of coronavirus disease and the importance of studying them from a gut-systemic perspective using multi-omics approaches.

Broad(er)-acting antiviral drugs, active against entire genera or families of viruses, should be developed and stockpiled in epidemic/pandemic peacetime. They can be used to counter outbreaks as soon as the new virus has been identified and will also remain important pharmacological tools after the introduction of vaccines and monoclonal antibodies.

Recombination is thought to be a mechanism that facilitates cross-species transmission in coronaviruses, thus acting as a driver of coronavirus spillover and emergence. Despite its significance, the mechanism of recombination is poorly understood, limiting our potential to estimate the risk of novel recombinant coronaviruses emerging in the future. As a tool for understanding recombination, here, we

Trained immunity is a long-term increase in responsiveness of innate immune cells, induced by certain infections and vaccines. During the last 3 years of the COVID-19 pandemic, vaccines that induce trained immunity, such as BCG, MMR, OPV, and others, have been investigated for their capacity to protect against COVID-19. Further, trained immunity-inducing vaccines have been shown to improve B and T cell

Although the development and clinical application of SARS-CoV-2 vaccines during the COVID-19 pandemic demonstrated unprecedented vaccine success in a short time frame, it also revealed a limitation of current vaccines in their inability to provide broad-spectrum or universal protection against emerging variants. Broad-spectrum vaccines, therefore, remain a dream and challenge for vaccinology. This

Different protein-delivery tools are being actively developed for efficient drug delivery into host cells. A recent study by Kreitz et al. in Nature reported a syringe-like protein delivery vector engineered from natural endosymbiotic bacteria for potential human use.

The use of bacterial colonists as therapy carriers is gaining interest for treating cancer. In a recent publication in Science, the work by Chen et al. proposes the engineering of a commensal bacterium of the human skin microbiota to cross-present tumor antigens to T cells and counteract tumor progression.