Selected Publications

Nat Immunol. 2020 Jun

Guanylate-binding proteins convert cytosolic bacteria into caspase-4 signaling platforms

Michal P. Wandel  1 , Bae-Hoon Kim2,3, Eui-Soon Park  2,3, Keith B. Boyle1 , Komal Nayak4,5, Brice Lagrange6, Adrian Herod7 , Thomas Henry  6, Matthias Zilbauer4,5, John Rohde7 , John D. MacMicking  2,3 and Felix Randow.

Bacterial lipopolysaccharide triggers human caspase-4 (murine caspase-11) to cleave gasdermin-D and induce pyroptotic cell death. How lipopolysaccharide sequestered in the membranes of cytosol-invading bacteria activates caspases remains unknown. Here we show that in interferon-γ-stimulated cells guanylate-binding proteins (GBPs) assemble on the surface of Gram-negative bacteria into polyvalent signaling platforms required for activation of caspase-4….Caspase-11 and GBPs epistatically protect mice against lethal bacterial challenge. Multiple antagonists of the pathway encoded by Shigella flexneri, a cytosol-adapted bacterium, provide compelling evolutionary evidence for the importance of the GBP–caspase-4 pathway in antibacterial defense.

Proc Natl Acad Sci. 2020 Apr

Salmonella expresses foreign genes during infection by degrading their silencer

Jeongjoon Choi, Eduardo Groisman.

Foreign genes confer new properties upon organisms. However, their expression often requires overcoming the silencing effects of the heat-stable nucleoid structuring (H-NS, also referred to as histone-like nucleoid structuring) protein, which binds to AT-rich foreign DNA in enteric bacteria. We establish that Salmonella enterica degrades H-NS when inside macrophages and that the resulting decrease in H-NS abundance de-represses foreign genes, even those not bound by antisilencing DNA-binding proteins. Conservation in the amino acid sequences of both the protease degrading H-NS and H-NS itself suggests that enteric bacteria share the uncovered strategy to express foreign genes silenced by H-NS.

Elife. 2020 Mar

Kimberley H GibsonFelipe TrajtenbergElsio A WunderMegan R BradyFabiana San MartinAriel MechalyZhiguo ShangJun LiuMathieu PicardeauAlbert KoAlejandro BuschiazzoCharles Vaughn Sindelar.

Spirochete bacteria, including important pathogens, exhibit a distinctive means of swimming via undulations of the entire cell. Motility is powered by the rotation of supercoiled ‘endoflagella’ that wrap around the cell body, confined within the periplasmic space. To investigate the structural basis of flagellar supercoiling, which is critical for motility, we determined the structure of native flagellar filaments from the spirochete Leptospira by integrating high-resolution cryo-electron tomography and X-ray crystallography. We show that these filaments are coated by a highly asymmetric, multi-component sheath layer, contrasting with flagellin-only homopolymers previously observed in exoflagellated bacteria. Distinct sheath proteins localize to the filament inner and outer curvatures to define the supercoiling geometry, explaining a key functional attribute of this spirochete flagellum.

PLoS Biol. 2019 Dec

High-order interactions distort the functional landscape of microbial consortia

Alicia Sanchez-Gorostiaga, Djordje Bajić, Melisa L. Osborne, Juan F. Poyatos, Alvaro Sanchez.

Understanding the link between community composition and function is a major challenge in microbial population biology, with implications for the management of natural microbiomes and the design of synthetic consortia. Specifically, it is poorly understood whether community functions can be quantitatively predicted from traits of species in monoculture. Inspired by the study of complex genetic interactions, we have examined how the amylolytic rate of combinatorial assemblages of six starch-degrading soil bacteria depend on the separate functional contributions from each species and their interactions….Our results suggest that the functional robustness of a consortium to pairwise and higher-order interactions critically affects our ability to predict and bottom-up engineer ecosystem function in complex communities.

Proteopedia 2019 -  2014 Jun

Malvankar Lab OmcS nanowire structure named one of the highest impact structures of the century

 2019 Jun

Functional characterization of a subtilisin-like serine protease from Vibrio cholerae.

Howell M1,2Dumitrescu DG1,2,3Blankenship LR1,2Herkert D1,2Hatzios SK4,2,3.

Vibrio cholerae, the causative agent of the human diarrheal disease cholera, exports numerous enzymes that facilitate its adaptation to both intestinal and aquatic niches. These secreted enzymes can mediate nutrient acquisition, biofilm assembly, and V. cholerae interactions with its host. We recently identified a V. cholerae-secreted serine protease, IvaP, that is active in V. cholerae-infected rabbits and human choleric stool. ….Here, we show that IvaP maturation requires a series of sequential N- and C-terminal cleavage events congruent with the enzyme’s mosaic protein domain structure. Using a catalytically inactive reporter protein, we determined that IvaP can be partially processed in trans, but intramolecular proteolysis is most likely required to generate the mature enzyme. Unlike many other subtilisin-like enzymes, the IvaP cleavage pattern is consistent with stepwise processing of the N-terminal propeptide, which could temporarily inhibit, and be cleaved by, the purified enzyme. Furthermore, IvaP was able to cleave purified intelectin, which inhibited intelectin binding to V. cholerae. These results suggest that IvaP plays a role in modulating intelectin-V. cholerae interactions.

 2019 Jun

Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis

Jutras BL1,2,3Lochhead RB4Kloos ZA1,5Biboy J6,7Strle K4Booth CJ8Govers SK1,2Gray J7Schumann P9Vollmer W6,7Bockenstedt LK10Steere AC4Jacobs-Wagner C11,2,3,12.

Lyme disease is a multisystem disorder caused by the spirochete Borrelia burgdorferi A common late-stage complication of this disease is oligoarticular arthritis, often involving the knee. In ∼10% of cases, arthritis persists after appropriate antibiotic treatment, leading to a proliferative synovitis typical of chronic inflammatory arthritides. Here, we provide evidence that peptidoglycan (PG), a major component of the B. burgdorferi cell envelope, may contribute to the development and persistence of Lyme arthritis (LA). We show that B. burgdorferi has a chemically atypical PG (PGBb) that is not recycled during cell-wall turnover. Instead, this pathogen sheds PGBb fragments into its environment during growth. Patients with LA mount a specific immunoglobulin G response against PGBb, which is significantly higher in the synovial fluid than in the serum of the same patient….Altogether, our study identifies PGBb as a likely contributor to inflammatory responses in LA. Persistence of this antigen in the joint may contribute to synovitis after antibiotics eradicate the pathogen. Furthermore, our finding that B. burgdorferi sheds immunogenic PGBb fragments during growth suggests a potential role for PGBb in the immunopathogenesis of other Lyme disease manifestations.

Nature. 2019 June

Mapping human microbiome drug metabolism by gut bacteria and their genes

Michael ZimmermannMaria Zimmermann-KogadeevaRebekka Wegmann & Andrew L. Goodman

Individuals vary widely in drug responses, which can be dangerous and expensive due to treatment delays and adverse effects. Growing evidence implicates the gut microbiome in this variability, however the molecular mechanisms remain largely unknown. Here we measured the ability of 76 diverse human gut bacteria to metabolize 271 oral drugs and found that many of these drugs are chemically modified by microbes. We combined high-throughput genetics with mass spectrometry to systematically identify drug-metabolizing microbial gene products. These microbiome-encoded enzymes can directly and significantly impact intestinal and systemic drug metabolism in mice and can explain drug-metabolizing activities of human gut bacteria and communities based on their genomic contents. These causal links between microbiota gene content and metabolic activities connect interpersonal microbiome variability to interpersonal differences in drug metabolism, which has implications for medical therapy and drug development across multiple disease indications.

Cell. 2019 May

Nucleoid Size Scaling and Intracellular Organization of Translation across Bacteria

William T.Gray129, Sander K.Govers139, YingjieXiang14, R.Parry13, ManuelCampos137, SangjinKim148, ChristineJacobs-Wagner135610

The scaling of organelles with cell size is thought to be exclusive to eukaryotes. Here, we demonstrate that similar scaling relationships hold for the bacterial nucleoid. Despite the absence of a nuclear membrane, nucleoid size strongly correlates with cell size, independent of changes in DNA amount and across various nutrient conditions. This correlation is observed in diverse bacteria, revealing a near-constant ratio between nucleoid and cell size for a given species. As in eukaryotes, the nucleocytoplasmic ratio in bacteria varies greatly among species. This spectrum of nucleocytoplasmic ratios is independent of genome size, and instead it appears linked to the average population cell size. Bacteria with different nucleocytoplasmic ratios have a cytoplasm with different biophysical properties, impacting ribosome mobility and localization. Together, our findings identify new organizational principles and biophysical features of bacterial cells, implicating the nucleocytoplasmic ratio and cell size as determinants of the intracellular organization of translation.

Cell. 2019 Apr

See also The New York TimesWired Bacteria Form Nature’s Power Grid: ‘We Have an Electric Planet’

Structure of microbial nanowires reveals stacked hemes that transport electrons over micrometers.

Fengbin Wang, Yangqi Gu, J. Patrick O’Brien, …, Allon I. Hochbaum, Edward H. Egelman, Nikhil S. Malvankar.

Long-range (>10 μm) transport of electrons along networks of Geobacter sulfurreducens protein filaments, known as microbial nanowires, has been invoked to explain a wide range of globally important redox phenomena. These nanowires were previously thought to be type IV pili composed of PilA protein. Here, we report a 3.7 Å resolution cryoelectron microscopy structure, which surprisingly reveals that, rather than PilA, G. sulfurreducens nanowires are assembled by micrometer-long polymerization of the hexaheme cytochrome OmcS, with hemes packed within ∼3.5–6 Å of each other. This structure explains the remarkable capacity of soil bacteria to transport electrons to remote electron acceptors for respiration and energy sharing.

 2019 Mar

Structural dynamics of bacteriophage P22 infection initiation revealed by cryo-electron tomography.

Wang C1,2,3Tu J3Liu J1,2,3Molineux IJ4.

For successful infection, bacteriophages must overcome multiple barriers to transport their genome and proteins across the bacterial cell envelope. We use cryo-electron tomography to study the infection initiation of phage P22 in Salmonella enterica serovar Typhimurium, revealing how a channel forms to allow genome translocation into the cytoplasm. Our results show free phages that initially attach obliquely to the cell through interactions between the O antigen and two of the six tailspikes; the tail needle also abuts the cell surface. The virion then orients perpendicularly and the needle penetrates the outer membrane. The needle is released and the internal head protein gp7* is ejected and assembles into an extracellular channel that extends from the gp10 baseplate to the cell surface. A second protein, gp20, is ejected and assembles into a structure that extends the extracellular channel across the outer membrane into the periplasm. Insertion of the third ejected protein, gp16, into the cytoplasmic membrane probably completes the overall trans-envelope channel into the cytoplasm. Construction of a trans-envelope channel is an essential step during infection of Gram-negative bacteria by all short-tailed phages, because such virions cannot directly deliver their genome into the cell cytoplasm.

 2019 Feb

Available energy fluxes drive a transition in the diversity, stability, and functional structure of microbial communities.

Marsland R 3rd1Cui W1,2Goldford J3Sanchez A4Korolev K1Mehta P1.

A fundamental goal of microbial ecology is to understand what determines the diversity, stability, and structure of microbial ecosystems. By analyzing a generalized consumer resource model that explicitly includes cross-feeding, stochastic colonization, and thermodynamics, we show that complex microbial communities generically exhibit a transition as a function of available energy fluxes from a “resource-limited” regime where community structure and stability is shaped by energetic and metabolic considerations to a diverse regime where the dominant force shaping microbial communities is the overlap between species’ consumption preferences. Our model reproduces large-scale ecological patterns observed across multiple experimental settings such as nestedness and differential beta diversity patterns along energy gradients.


Activity-Based Protein Profiling at the Host-Pathogen Interface.

Kovalyova Y1,2Hatzios SK3,4,5.

Activity-based protein profiling (ABPP) is a technique for selectively detecting reactive amino acids in complex proteomes with the aid of chemical probes. Using probes that target catalytically active enzymes, ABPP can rapidly define the functional proteome of a biological system. In recent years, this approach has been increasingly applied to globally profile enzymes active at the host-pathogen interface of microbial infections. From in vitro co-culture systems to animal models of infection, these studies have revealed enzyme-mediated mechanisms of microbial pathogenicity, host immunity, and metabolic adaptation that dynamically shape pathogen interactions with the host.

 2019 Feb

Separating host and microbiome contributions to drug pharmacokinetics and toxicity.

Zimmermann M#1Zimmermann-Kogadeeva M#1Wegmann R1Goodman AL2.

The gut microbiota is implicated in the metabolism of many medical drugs, with consequences for interpersonal variation in drug efficacy and toxicity. However, quantifying microbial contributions to drug metabolism is challenging, particularly in cases where host and microbiome perform the same metabolic transformation. We combined gut commensal genetics with gnotobiotics to measure brivudine drug metabolism across tissues in mice that vary in a single microbiome-encoded enzyme. Informed by these measurements, we built a pharmacokinetic model that quantitatively predicts microbiome contributions to systemic drug and metabolite exposure, as a function of bioavailability, host and microbial drug-metabolizing activity, drug and metabolite absorption, and intestinal transit kinetics. Clonazepam studies illustrate how this approach disentangles microbiome contributions to metabolism of drugs subject to multiple metabolic routes and transformations.

 2018 Dec

Dietary sugar silences a colonization factor in a mammalian gut symbiont.

Townsend GE 2nd1,2Han W1,2Schwalm ND 3rd1,2Raghavan V1,2Barry NA1,2Goodman AL1,2Groisman EA3,2.

Dietary components are believed to influence the composition of the gut microbiota by serving as nutrients to a subset of microbes, thereby favoring their expansion. However, we now report that dietary fructose and glucose, which are prevalent in the Western diet, specifically silence a protein that is necessary for gut colonization, but not for utilization of these sugars, by the human gut commensal Bacteroides thetaiotaomicron. Our findings underscore a role for dietary sugars that escape absorption by the host intestine and reach the microbiota: regulation of gut colonization by beneficial microbes independently of supplying nutrients to the microbiota.

 2018 Nov

Cryo-electron tomography of periplasmic flagella in Borrelia burgdorferi reveals a distinct cytoplasmic ATPase complex.

Qin Z1,2Tu J2Lin T2Norris SJ2Li C3Motaleb MA4Liu J1,2.

Periplasmic flagella are essential for the distinct morphology and motility of spirochetes. Our studies provide structural insights into the unique mechanisms underlying assembly and rotation of the periplasmic flagella and may provide the basis for the development of novel therapeutic strategies against several pathogenic spirochetes.

 2018 Nov

De novo design of self-assembling helical protein filaments.

Shen H1,2,3Fallas JA4,2Lynch E2Sheffler W1,2Parry B5,6Jannetty N6,7Decarreau J8Wagenbach M8Vicente JJ8Chen J9,10Wang L10,11Dowling Q2,12Oberdorfer G1,2Stewart L1Wordeman L8De Yoreo J9,10Jacobs-Wagner C6,7,13Kollman J2Baker D4,2,14.

We describe a general computational approach to designing self-assembling helical filaments from monomeric proteins and use this approach to design proteins that assemble into micrometer-scale filaments with a wide range of geometries in vivo and in vitro. The ability to generate dynamic, highly ordered structures that span micrometers from protein monomers opens up possibilities for the fabrication of new multiscale metamaterials.

 2018 Nov

Mucosal homeostasis is altered in the ileum of gnotobiotic mice.

Greig CJ1Alper A2Goodman AL3Cowles RA4.

Single-organism gnotobiotic mice demonstrate enhanced morphometric parameters compared with mice with CF and show differences in growth patterns among bacterial species. These findings suggest unique interactions between individual bacteria and the host animal which hold potential for future therapeutic strategies aimed at mucosal restoration. The mechanisms involved in this process therefore warrant further study.

 2018 Nov

A tetratricopeptide repeat domain protein has profound effects on assembly of periplasmic flagella, morphology and motility of the lyme disease spirochete Borrelia burgdorferi.

Moon KH1Zhao X2Xu H1Liu J2,3Motaleb MA1.

Spirochetes possess a unique periplasmic flagellar motor component called the collar. To identify a collar protein, we have inactivated almost all genes annotated as motility-related in the Borrelia burgdorferi genome and identified only FlbB, which comprises the base of the collar. Using various comprehensive approaches, we identified a tetratricopeptide repeat protein BB0236 as a potential candidate for the collar. Biochemical assays indicated that FlbB interacts with BB0236. Furthermore, ∆bb0236 mutant analyses indicated that BB0236 is crucial for collar structure assembly, cellular morphology, motility, orientation of periplasmic flagella and assembly of other flagellar structures. Together, our studies provide new insights into the organization and the complex assembly inherent to the unique spirochetal collar structure.

 2018 Oct

On the deformability of an empirical fitness landscape by microbial evolution.

Bajić D1,2Vila JCC3,2Blount ZD4,5,6Sánchez A1,2.

A fitness landscape is a map between the genotype and its reproductive success in a given environment. The topography of fitness landscapes largely governs adaptive dynamics, constraining evolutionary trajectories and the predictability of evolution. Here we have systematically characterized the deformability of the genome-wide metabolic fitness landscape of the bacterium Escherichia coli. Our results suggest that, even in situations in which mutations have strong environmental effects, fitness landscapes may retain their power to forecast evolution over small mutational distances despite the potential attenuation of that power over longer evolutionary trajectories. Our methods and results provide an avenue for integrating adaptive and eco-evolutionary dynamics with complex genetics and genomics.

 2018 Oct

Visualization of the type III secretion mediated Salmonella-host cell interface using cryo-electron tomography.

Park D1,2Lara-Tejero M1Waxham MN3Li W1,2Hu B4,5Galán JE1Liu J1,2,4.

Many important gram-negative bacterial pathogens use highly sophisticated type III protein secretion systems (T3SSs) to establish complex host-pathogen interactions. Here, we use high-throughput cryo-electron tomography (cryo-ET) to visualize the T3SS-mediated Salmonella-host cell interface. Our analysis reveals the intact translocon at an unprecedented level of resolution, its deployment in the host cell membrane, and the establishment of an intimate association between the bacteria and the target cells, which is essential for effector translocation. Our studies provide critical data supporting the long postulated direct injection model for effector translocation.

 2018 Oct

Characterization of fluorescent proteins, promoters, and selectable markers for applications in the Lyme disease spirochete Borrelia burgdorferi.

Takacs CN1,2,3Kloos ZA1,4Scott M1,2,3Rosa PA5Jacobs-Wagner C6,2,3,7.

Genetic manipulation of the Lyme disease spirochete B. burgdorferi remains cumbersome, despite significant progress in the field. Of interest, B. burgdorferi displays complex cellular organization features that have yet to be understood. Here, we complement and expand the array of molecular tools available for use in B. burgdorferi by generating and characterizing multiple fluorescent proteins, antibiotic selection markers, and promoters of varied strengths. These tools will facilitate investigations in this important human pathogen, as exemplified by the polar and midcell localization of the cell envelope regulator BB0323, which we uncovered using these reagents.

Curr Top Microbiol Immunol.   2018 Sep  

Activity-Based Protein Profiling at the Host-Pathogen Interface.

Kovalyova Y1,2Hatzios SK3,4,5.

Activity-based protein profiling (ABPP) is a technique for selectively detecting reactive amino acids in complex proteomes with the aid of chemical probes. Using probes that target catalytically active enzymes, ABPP can rapidly define the functional proteome of a biological system. In recent years, this approach has been increasingly applied to globally profile enzymes active at the host-pathogen interface of microbial infections. From in vitro co-culture systems to animal models of infection, these studies have revealed enzyme-mediated mechanisms of microbial pathogenicity, host immunity, and metabolic adaptation that dynamically shape pathogen interactions with the host.

Elife.  2018 Sep 

Human gut Bacteroides capture vitamin B12 via cell surface-exposed lipoproteins.

Wexler AG1,2Schofield WB1,2Degnan PH1,2Folta-Stogniew E3Barry NA1,2Goodman AL1,2.

Human gut Bacteroides use surface-exposed lipoproteins to bind and metabolize complex polysaccharides. Although vitamins and other nutrients are also essential for commensal fitness, much less is known about how commensal bacteria compete with each other or the host for these critical resources. Our studies suggest that Bacteroides use surface-exposed lipoproteins not only for capturing polysaccharides, but also to acquire key vitamins in the gut.

 2018 Aug 

Emergent simplicity in microbial community assembly.

Goldford JE1,2Lu N3Bajić D3Estrela S3Tikhonov M4,5Sanchez-Gorostiaga A3Segrè D1,6,7Mehta P8,7Sanchez A9,3.

A major unresolved question in microbiome research is whether the complex taxonomic architectures observed in surveys of natural communities can be explained and predicted by fundamental, quantitative principles. Bridging theory and experiment is hampered by the multiplicity of ecological processes that simultaneously affect community assembly in natural ecosystems. We addressed this challenge by monitoring the assembly of hundreds of soil- and plant-derived microbiomes in well-controlled minimal synthetic media. Both the community-level function and the coarse-grained taxonomy of the resulting communities are highly predictable and governed by nutrient availability, despite substantial species variability. By generalizing classical ecological models to include widespread nonspecific cross-feeding, we show that these features are all emergent properties of the assembly of large microbial communities, explaining their ubiquity in natural microbiomes.

 2018 Jul

protein that controls the onset of a Salmonella virulence program.

Yeom J1, Pontes MH1,2, Choi J1, Groisman EA3,2.

The mechanism of action and contribution to pathogenesis of many virulence genes are understood. By contrast, little is known about anti-virulence genes, which contribute to the start, progression, and outcome of an infection. We now report how an anti-virulence factor in Salmonella enterica serovar Typhimurium dictates the onset of a genetic program that governs metabolic adaptations and pathogen survival in host tissues.

 2018 Jul

The Stringent Response Determines the Ability of a Commensal Bacterium to Survive Starvation and to Persist in the Gut.

Schofield WB1, Zimmermann-Kogadeeva M1, Zimmermann M1, Barry NA1, Goodman AL2.

In the mammalian gut, bacteria compete for resources to maintain their populations, but the factors determining their success are poorly understood. We report that the human gut bacterium Bacteroides thetaiotaomicron relies on the stringent response, an intracellular signaling pathway that allocates resources away from growth, to survive carbon starvation and persist in the gut.

 2018 Jun

Genomewide phenotypic analysis of growthcell morphogenesis, and cell cycle events in Escherichia coli.

Campos M1,2,3,4, Govers SK1,2, Irnov I1,2, Dobihal GS1,3, Cornet F4, Jacobs-Wagner C5,2,3,6.

Cell size, cell growth, and cell cycle events are necessarily intertwined to achieve robust bacterial replication. Yet, a comprehensive and integrated view of these fundamental processes is lacking. Here, we describe an image-based quantitative screen of the single-gene knockout collection of Escherichia coli and identify many new genes involved in cell morphogenesis, population growth, nucleoid (bulk chromosome) dynamics, and cell division.

 2018 Jun

unique cytoplasmic ATPase complex defines the Legionella pneumophila type IV secretionchannel.

Chetrit D1, Hu B2,3, Christie PJ2, Roy CR4, Liu J5,6,7.

Type IV secretion systems (T4SSs) are complex machines used by bacteria to deliver protein and DNA complexes into target host cells1-5. Conserved ATPases are essential for T4SS function, but how they coordinate their activities to promote substrate transfer remains poorly understood. Here, we show that the DotB ATPase associates with the Dot-Icm T4SS at the Legionella cell pole through interactions with the DotO ATPase.

 2018 May

Reduction in adaptor amounts establishes degradation hierarchy among protease substrates.

Yeom J1, Gao X1, Groisman EA2,3.

ATP-dependent proteases control critical cellular processes, including development, physiology, and virulence. A given protease may recognize a substrate directly via an unfoldase domain or subunit or indirectly via an adaptor that delivers the substrate to the unfoldase. We now report that cells achieve differential stability among substrates of a given protease by modulating adaptor amounts.

 2018 May

Distribution of Initiation Times Reveals Mechanisms of Transcriptional Regulation in Single Cells.

Choubey S1, Kondev J1, Sanchez A2.

Transcription is the dominant point of control of gene expression. Biochemical studies have revealed key molecular components of transcription and their interactions, but the dynamics of transcription initiation in cells is still poorly understood. This state of affairs is being remedied with experiments that observe transcriptional dynamics in single cells using fluorescent reporters.

 2018 May

Topical application of aminoglycoside antibiotics enhances host resistance to viral infections in a microbiota-independent manner.

Gopinath S1,2, Kim MV2, Rakib T2, Wong PW2, van Zandt M3, Barry NA4, Kaisho T5, Goodman AL1,4, Iwasaki A6,7.

Antibiotics are widely used to treat infections in humans. However, the impact of antibiotic use on host cells is understudied. Here we identify an antiviral effect of commonly used aminoglycoside antibiotics. We show that topical mucosal application of aminoglycosides prophylactically increased host resistance to a broad range of viral infections including herpes simplex viruses, influenza A virus and Zika virus. 

Cell. 2018 Mar

Subcellular Organization: A Critical Feature of Bacterial Cell Replication.

Surovtsev IV1, Jacobs-Wagner C2.

Spatial order is required for faithful and efficient cellular replication and offers a powerful means for the development of unique biological properties. Here, we discuss organizational features of bacterial cells and highlight how bacteria have evolved diverse spatial mechanisms to overcome challenges cells face as self-replicating entities.

Combinatorial Gene Regulation through Kinetic Control of the Transcription Cycle.

Expressing the Geobacter metallireducens PilA in Geobacter sulfurreducens Yields Pili with Exceptional Conductivity.

Engineering Regulatory Systems Modulate Gene Expression of Human Commensals in the Gut.

An insider’s perspective: Bacteroides as a window into the microbiome.

Replication fork passage drives asymmetric dynamics of a critical nucleoid-associated protein in Caulobacter.

DNA-relay mechanism is sufficient to explain ParA-dependent intracellular transport and patterning of single and multiple cargos.

Lyme disease and relapsing fever Borrelia elongate through zones of peptidoglycan synthesis that mark division sites of daughter cells.

Reducing Ribosome Biosynthesis Promotes Translation during Low Mg2+ Stress.

Multiple Signals Govern Utilization of a Polysaccharide in the Gut Bacterium Bacteroides thetaiotaomicron.

Feedback Control of Two-Component Regulatory Systems

Learning from the Leaders: Gene Regulation by the Transcription Termination Factor Rho.

Acidic pH sensing in the bacterial cytoplasm is required for Salmonella virulence.

Human symbionts inject and neutralize antibacterial toxins to persist in the gut.

Combinatorial Gene Regulation through Kinetic Control of the Transcription Cycle.