Showing papers on "Bacteria published in 2019"

GABA-modulating bacteria of the human gut microbiota

Abstract: The gut microbiota affects many important host functions, including the immune response and the nervous system1. However, while substantial progress has been made in growing diverse microorganisms of the microbiota2, 23-65% of species residing in the human gut remain uncultured3,4, which is an obstacle for understanding their biological roles. A likely reason for this unculturability is the absence in artificial media of key growth factors that are provided by neighbouring bacteria in situ5,6. In the present study, we used co-culture to isolate KLE1738, which required the presence of Bacteroides fragilis to grow. Bioassay-driven purification of B. fragilis supernatant led to the isolation of the growth factor, which, surprisingly, is the major inhibitory neurotransmitter GABA (γ-aminobutyric acid). GABA was the only tested nutrient that supported the growth of KLE1738, and a genome analysis supported a GABA-dependent metabolism mechanism. Using growth of KLE1738 as an indicator, we isolated a variety of GABA-producing bacteria, and found that Bacteroides ssp. produced large quantities of GABA. Genome-based metabolic modelling of the human gut microbiota revealed multiple genera with the predicted capability to produce or consume GABA. A transcriptome analysis of human stool samples from healthy individuals showed that GABA-producing pathways are actively expressed by Bacteroides, Parabacteroides and Escherichia species. By coupling 16S ribosmal RNA sequencing with functional magentic resonance imaging in patients with major depressive disorder, a disease associated with an altered GABA-mediated response, we found that the relative abundance levels of faecal Bacteroides are negatively correlated with brain signatures associated with depression.

A new antibiotic selectively kills Gram-negative pathogens

Abstract: The current need for novel antibiotics is especially acute for drug-resistant Gram-negative pathogens1,2. These microorganisms have a highly restrictive permeability barrier, which limits the penetration of most compounds3,4. As a result, the last class of antibiotics that acted against Gram-negative bacteria was developed in the 1960s2. We reason that useful compounds can be found in bacteria that share similar requirements for antibiotics with humans, and focus on Photorhabdus symbionts of entomopathogenic nematode microbiomes. Here we report a new antibiotic that we name darobactin, which was obtained using a screen of Photorhabdus isolates. Darobactin is coded by a silent operon with little production under laboratory conditions, and is ribosomally synthesized. Darobactin has an unusual structure with two fused rings that form post-translationally. The compound is active against important Gram-negative pathogens both in vitro and in animal models of infection. Mutants that are resistant to darobactin map to BamA, an essential chaperone and translocator that folds outer membrane proteins. Our study suggests that bacterial symbionts of animals contain antibiotics that are particularly suitable for development into therapeutics.

Relationship Between Biofilm Formation and Antimicrobial Resistance in Gram-Negative Bacteria.

Abstract: Gram-negative microorganisms are a significant cause of infection in both community and nosocomial settings. The increase, emergence, and spread of antimicrobial resistance among bacteria are the most important health problems worldwide. One of the mechanisms of resistance used by bacteria is biofilm formation, which is also a mechanism of virulence. This study analyzed the possible relationship between antimicrobial resistance and biofilm formation among isolates of three Gram-negative bacteria species. Several relationships were found between the ability to form biofilm and antimicrobial resistance, being different for each species. Indeed, gentamicin and ceftazidime resistance was related to biofilm formation in Escherichia coli, piperacillin/tazobactam, and colistin in Klebsiella pneumoniae, and ciprofloxacin in Pseudomonas aeruginosa. However, no relationship was observed between global resistance or multidrug-resistance and biofilm formation. In addition, compared with other reported data, the isolates in the present study showed higher rates of antimicrobial resistance. In conclusion, the acquisition of specific antimicrobial resistance can compromise or enhance biofilm formation in several species of Gram-negative bacteria. However, multidrug-resistant isolates do not show a trend to being greater biofilm producers than non-multiresistant isolates.

Roles of plant volatiles in defence against microbial pathogens and microbial exploitation of volatiles

Abstract: Plants emit a large variety of volatile organic compounds during infection by pathogenic microbes, including terpenes, aromatics, nitrogen-containing compounds, and fatty acid derivatives, as well as the volatile plant hormones, methyl jasmonate, and methyl salicylate. Given the general antimicrobial activity of plant volatiles and the timing of emission following infection, these compounds have often been assumed to function in defence against pathogens without much solid evidence. In this review, we critically evaluate current knowledge on the toxicity of volatiles to fungi, bacteria, and viruses and their role in plant resistance as well as how they act to induce systemic resistance in uninfected parts of the plant and in neighbouring plants. We also discuss how microbes can detoxify plant volatiles and exploit them as nutrients, attractants for insect vectors, and inducers of volatile emissions, which stimulate immune responses that make plants more susceptible to infection. Although much more is known about plant volatile-herbivore interactions, knowledge of volatile-microbe interactions is growing and it may eventually be possible to harness plant volatiles to reduce disease in agriculture and forestry. Future research in this field can be facilitated by making use of the analytical and molecular tools generated by the prolific research on plant-herbivore interactions.

Antibacterial Activity and Mechanisms of Essential Oil from Citrus medica L. var. sarcodactylis.

Abstract: In this work, antibacterial activity of finger citron essential oil (FCEO, Citrus medica L. var. sarcodactylis) and its mechanism against food-borne bacteria were evaluated. A total of 28 components in the oil were identified by gas chromatography-mass spectrometry, in which limonene (45.36%), γ-terpinene (21.23%), and dodecanoic acid (7.52%) were three main components. For in vitro antibacterial tests, FCEO exhibited moderately antibacterial activity against common food-borne bacteria: Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Micrococcus luteus. It showed a better bactericidal effect on Gram-positive bacteria than Gram-negative. Mechanisms of the antibacterial action were investigated by observing changes of bacteria morphology according to scanning electron microscopy, time-kill analysis, and permeability of cell and membrane integrity. Morphology of tested bacteria was changed and damaged more seriously with increased concentration and exposure time of FCEO. FCEO showed a significant reduction effect on the growth rate of surviving bacteria and lead to lysis of the cell wall, intracellular ingredient leakage, and consequently, cell death.

Epistasis between antibiotic tolerance, persistence, and resistance mutations.

Abstract: Understanding the evolution of microorganisms under antibiotic treatments is a burning issue. Typically, several resistance mutations can accumulate under antibiotic treatment, and the way in which resistance mutations interact, i.e., epistasis, has been extensively studied. We recently showed that the evolution of antibiotic resistance in Escherichia coli is facilitated by the early appearance of tolerance mutations. In contrast to resistance, which reduces the effectiveness of the drug concentration, tolerance increases resilience to antibiotic treatment duration in a nonspecific way, for example when bacteria transiently arrest their growth. Both result in increased survival under antibiotics, but the interaction between resistance and tolerance mutations has not been studied. Here, we extend our analysis to include the evolution of a different type of tolerance and a different antibiotic class and measure experimentally the epistasis between tolerance and resistance mutations. We derive the expected model for the effect of tolerance and resistance mutations on the dynamics of survival under antibiotic treatment. We find that the interaction between resistance and tolerance mutations is synergistic in strains evolved under intermittent antibiotic treatment. We extend our analysis to mutations that result in antibiotic persistence, i.e., to tolerance that is conferred only on a subpopulation of cells. We show that even when this population heterogeneity is included in our analysis, a synergistic interaction between antibiotic persistence and resistance mutations remains. We expect our general framework for the epistasis in killing conditions to be relevant for other systems as well, such as bacteria exposed to phages or cancer cells under treatment.

The Role of Iron and Siderophores in Infection, and the Development of Siderophore Antibiotics

Abstract: Iron is an essential nutrient for bacterial growth, replication, and metabolism. Humans store iron bound to various proteins such as hemoglobin, haptoglobin, transferrin, ferritin, and lactoferrin, limiting the availability of free iron for pathogenic bacteria. However, bacteria have developed various mechanisms to sequester or scavenge iron from the host environment. Iron can be taken up by means of active transport systems that consist of bacterial small molecule siderophores, outer membrane siderophore receptors, the TonB-ExbBD energy-transducing proteins coupling the outer and the inner membranes, and inner membrane transporters. Some bacteria also express outer membrane receptors for iron-binding proteins of the host and extract iron directly from these for uptake. Ultimately, iron is acquired and transported into the bacterial cytoplasm. The siderophores are small molecules produced and released by nearly all bacterial species and are classified according to the chemical nature of their iron-chelating group (ie, catechol, hydroxamate, α-hydroxyl-carboxylate, or mixed types). Siderophore-conjugated antibiotics that exploit such iron-transport systems are under development for the treatment of infections caused by gram-negative bacteria. Despite demonstrating high in vitro potency against pathogenic multidrug-resistant bacteria, further development of several candidates had stopped due to apparent adaptive resistance during exposure, lack of consistent in vivo efficacy, or emergence of side effects in the host. However, cefiderocol, with an optimized structure, has advanced and has been investigated in phase 1 to 3 clinical trials. This article discusses the mechanisms implicated in iron uptake and the challenges associated with the design and utilization of siderophore-mimicking antibiotics.

Sources of artifact in measurements of 6mA and 4mC abundance in eukaryotic genomic DNA.

Abstract: Directed DNA methylation on N6-adenine (6mA), N4-cytosine (4mC), and C5-cytosine (5mC) can potentially increase DNA coding capacity and regulate a variety of biological functions. These modifications are relatively abundant in bacteria, occurring in about a percent of all bases of most bacteria. Until recently, 5mC and its oxidized derivatives were thought to be the only directed DNA methylation events in metazoa. New and more sensitive detection techniques (ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-ms/ms) and single molecule real-time sequencing (SMRTseq)) have suggested that 6mA and 4mC modifications could be present in a variety of metazoa. Here, we find that both of these techniques are prone to inaccuracies, which overestimate DNA methylation concentrations in metazoan genomic DNA. Artifacts can arise from methylated bacterial DNA contamination of enzyme preparations used to digest DNA and contaminating bacterial DNA in eukaryotic DNA preparations. Moreover, DNA sonication introduces a novel modified base from 5mC that has a retention time near 4mC that can be confused with 4mC. Our analyses also suggest that SMRTseq systematically overestimates 4mC in prokaryotic and eukaryotic DNA and 6mA in DNA samples in which it is rare. Using UHPLC-ms/ms designed to minimize and subtract artifacts, we find low to undetectable levels of 4mC and 6mA in genomes of representative worms, insects, amphibians, birds, rodents and primates under normal growth conditions. We also find that mammalian cells incorporate exogenous methylated nucleosides into their genome, suggesting that a portion of 6mA modifications could derive from incorporation of nucleosides from bacteria in food or microbiota. However, gDNA samples from gnotobiotic mouse tissues found rare (0.9–3.7 ppm) 6mA modifications above background. Altogether these data demonstrate that 6mA and 4mC are rarer in metazoa than previously reported, and highlight the importance of careful sample preparation and measurement, and need for more accurate sequencing techniques.

Sepsis: mechanisms of bacterial injury to the patient

Abstract: In bacteremia the majority of bacterial species are killed by oxidation on the surface of erythrocytes and digested by local phagocytes in the liver and the spleen. Sepsis-causing bacteria overcome this mechanism of human innate immunity by versatile respiration, production of antioxidant enzymes, hemolysins, exo- and endotoxins, exopolymers and other factors that suppress host defense and provide bacterial survival. Entering the bloodstream in different forms (planktonic, encapsulated, L-form, biofilm fragments), they cause different types of sepsis (fulminant, acute, subacute, chronic, etc.). Sepsis treatment includes antibacterial therapy, support of host vital functions and restore of homeostasis. A bacterium killing is only one of numerous aspects of antibacterial therapy. The latter should inhibit the production of bacterial antioxidant enzymes and hemolysins, neutralize bacterial toxins, modulate bacterial respiration, increase host tolerance to bacterial products, facilitate host bactericidal mechanism and disperse bacterial capsule and biofilm.

The distinction of CPR bacteria from other bacteria based on protein family content

Abstract: Candidate phyla radiation (CPR) bacteria separate phylogenetically from other bacteria, but the organismal distribution of their protein families remains unclear. Here, we leveraged sequences from thousands of uncultivated organisms and identified protein families that co-occur in genomes, thus are likely foundational for lineage capacities. Protein family presence/absence patterns cluster CPR bacteria together, and away from all other bacteria and archaea, partly due to proteins without recognizable homology to proteins in other bacteria. Some are likely involved in cell-cell interactions and potentially important for episymbiotic lifestyles. The diversity of protein family combinations in CPR may exceed that of all other bacteria. Over the bacterial tree, protein family presence/absence patterns broadly recapitulate phylogenetic structure, suggesting persistence of core sets of proteins since lineage divergence. The CPR could have arisen in an episode of dramatic but heterogeneous genome reduction or from a protogenote community and co-evolved with other bacteria.

Nanoscale Bacteria‐Enabled Autonomous Drug Delivery System (NanoBEADS) Enhances Intratumoral Transport of Nanomedicine

Abstract: Cancer drug delivery remains a formidable challenge due to systemic toxicity and inadequate extravascular transport of nanotherapeutics to cells distal from blood vessels. It is hypothesized that, in absence of an external driving force, the Salmonella enterica serovar Typhimurium could be exploited for autonomous targeted delivery of nanotherapeutics to currently unreachable sites. To test the hypothesis, a nanoscale bacteria-enabled autonomous drug delivery system (NanoBEADS) is developed in which the functional capabilities of the tumor-targeting S. Typhimurium VNP20009 are interfaced with poly(lactic-co-glycolic acid) nanoparticles. The impact of nanoparticle conjugation is evaluated on NanoBEADS' invasion of cancer cells and intratumoral transport in 3D tumor spheroids in vitro, and biodistribution in a mammary tumor model in vivo. It is found that intercellular (between cells) self-replication and translocation are the dominant mechanisms of bacteria intratumoral penetration and that nanoparticle conjugation does not impede bacteria's intratumoral transport performance. Through the development of new transport metrics, it is demonstrated that NanoBEADS enhance nanoparticle retention and distribution in solid tumors by up to a remarkable 100-fold without requiring any externally applied driving force or control input. Such autonomous biohybrid systems could unlock a powerful new paradigm in cancer treatment by improving the therapeutic index of chemotherapeutic drugs and minimizing systemic side effects.

Engineered toxin-intein antimicrobials can selectively target and kill antibiotic-resistant bacteria in mixed populations.

Abstract: Targeted killing of pathogenic bacteria without harming beneficial members of host microbiota holds promise as a strategy to cure disease and limit both antimicrobial-related dysbiosis and development of antimicrobial resistance. We engineer toxins that are split by inteins and deliver them by conjugation into a mixed population of bacteria. Our toxin-intein antimicrobial is only activated in bacteria that harbor specific transcription factors. We apply our antimicrobial to specifically target and kill antibiotic-resistant Vibrio cholerae present in mixed populations. We find that 100% of antibiotic-resistant V. cholerae receiving the plasmid are killed. Escape mutants were extremely rare (10-6-10-8). We show that conjugation and specific killing of targeted bacteria occurs in the microbiota of zebrafish and crustacean larvae, which are natural hosts for Vibrio spp. Toxins split with inteins could form the basis of precision antimicrobials to target pathogens that are antibiotic resistant.

An interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp.

Abstract: Bacteria have evolved sophisticated mechanisms to inhibit the growth of competitors1. One such mechanism involves type VI secretion systems, which bacteria can use to inject antibacterial toxins directly into neighbouring cells. Many of these toxins target the integrity of the cell envelope, but the full range of growth inhibitory mechanisms remains unknown2. Here we identify a type VI secretion effector, Tas1, in the opportunistic pathogen Pseudomonas aeruginosa. The crystal structure of Tas1 shows that it is similar to enzymes that synthesize (p)ppGpp, a broadly conserved signalling molecule in bacteria that modulates cell growth rate, particularly in response to nutritional stress3. However, Tas1 does not synthesize (p)ppGpp; instead, it pyrophosphorylates adenosine nucleotides to produce (p)ppApp at rates of nearly 180,000 molecules per minute. Consequently, the delivery of Tas1 into competitor cells drives rapid accumulation of (p)ppApp, depletion of ATP, and widespread dysregulation of essential metabolic pathways, thereby resulting in target cell death. Our findings reveal a previously undescribed mechanism for interbacterial antagonism and demonstrate a physiological role for the metabolite (p)ppApp in bacteria.

Polymyxin Derivatives that Sensitize Gram-Negative Bacteria to Other Antibiotics

Abstract: Polymyxins (polymyxin B (PMB) and polymyxin E (colistin)) are cyclic lipodecapeptide antibiotics, highly basic due to five free amino groups, and rapidly bactericidal against Gram-negative bacteria, such as the majority of Enterobacteriaceae as well as Acinetobacter baumannii and Pseudomonas aeruginosa. Their clinical use was abandoned in the 1960s because of nephrotoxicity and because better-tolerated drugs belonging to other antibiotic classes were introduced. Now, due to the global dissemination of extremely-drug resistant Gram-negative bacterial strains, polymyxins have resurged as the last-line drugs against those strains. Novel derivatives that are less toxic and/or more effective at tolerable doses are currently under preclinical development and their properties have recently been described in several extensive reviews. Other derivatives lack any direct bactericidal activity but damage the outermost permeability barrier, the outer membrane, of the target bacteria and make it more permeable to many other antibiotics. This review describes the properties of three thus far best-characterized “permeabilizer” derivatives, i.e., the classic permeabilizer polymyxin B nonapeptide (PMBN), NAB7061, and SPR741/NAB741, a compound that recently successfully passed the clinical phase 1. Also, a few other permeabilizer compounds are brought up.

Pathogen-Specific Polymeric Antimicrobials with Significant Membrane Disruption and Enhanced Photodynamic Damage To Inhibit Highly Opportunistic Bacteria

Abstract: Highly pathogenic Gram-negative bacteria and their drug resistance are a severe public health threat with high mortality. Gram-negative bacteria are hard to kill due to the complex cell envelopes with low permeability and extra defense mechanisms. It is challenging to treat them with current strategies, mainly including antibiotics, peptides, polymers, and some hybrid materials, which still face the issue of drug resistance, limited antibacterial selectivity, and severe side effects. Together with precise bacteria targeting, synergistic therapeutic modalities, including physical membrane damage and photodynamic eradication, are promising to combat Gram-negative bacteria. Herein, pathogen-specific polymeric antimicrobials were formulated from amphiphilic block copolymers, poly(butyl methacrylate)- b-poly(2-(dimethylamino) ethyl methacrylate- co-eosin)- b-ubiquicidin, PBMA- b-P(DMAEMA- co-EoS)-UBI, in which pathogen-targeting peptide ubiquicidin (UBI) was tethered in the hydrophilic chain terminal, and Eosin-Y was copolymerized in the hydrophilic block. The micelles could selectively adhere to bacteria instead of mammalian cells, inserting into the bacteria membrane to induce physical membrane damage and out-diffusion of intracellular milieu. Furthermore, significant in situ generation of reactive oxygen species was observed upon light irradiation, achieving further photodynamic eradication. Broad-spectrum bacterial inhibition was demonstrated for the polymeric antimicrobials, especially highly opportunistic Gram-negative bacteria, such as Pseudomona aeruginosa ( P. aeruginosa) based on the synergy of physical destruction and photodynamic therapy, without detectable resistance. In vivo P. aeruginosa-infected knife injury model and burn model both proved good potency of bacteria eradication and promoted wound healing, which was comparable with commercial antibiotics, yet no risk of drug resistance. It is promising to hurdle the infection and resistance suffered from highly opportunistic bacteria.

Effects of Plant Growth-Promoting Bacteria (PGPB) Inoculation on the Growth, Antioxidant Activity, Cu Uptake, and Bacterial Community Structure of Rape (Brassica napus L.) Grown in Cu-Contaminated Agricultural Soil.

Abstract: Previous analyses of plant growth-promoting bacteria (PGPB) combined with the remediation of heavy metal pollution in soil have largely been performed under potting or greenhouse conditions, and in situ remediation experiments under field conditions have rarely been reported. In this study, the effects of the metal-resistant PGPB Microbacterium oxydans JYC17, Pseudomonas thivervalensis Y1-3-9, and Burkholderia cepacia J62 on soil Cu pollution under rape remediation were studied in the farmland surrounding the Nanjing Jiuhuashan copper mining region in China. Following inoculation treatment for 50 days, the biomasses of the rape inoculated with strains JYC17, Y1-3-9, and J62 increased, and the total amounts of Cu uptake increased by 113.38, 66.26, and 67.91%, respectively, the translocation factor (TF) of rape inoculated with J62 was 0.85, a significant increase of 70.68%, thus improving the Cu remediation efficiency of the rape. Y1-3-9 and J62 affected the bioavailability of Cu in the soil, and the water-soluble Cu contents were increased by 10.13 and 41.77%, respectively, compared with the control. The antioxidant activities in the rape leaves showed that the tested bacteria increased the contents of antioxidant non-enzymatic substances, including ascorbic acid (ASA) and glutathione (GSH), which were increased by 40.24-91.22% and 9.89-17.67%, respectively, thereby reducing the oxidative stress caused by heavy metals and the contents of thiobarbituric acid-reactive substances (TBARS) and peroxidase (POD). PCR-denaturing gradient gel electrophoresis (PCR-DGGE) was used to analyze the effects of the tested bacteria on the cultivation-dependent and cultivation-independent bacterial communities in the root endosphere and rhizosphere soil of the rape. The sequencing results of the DGGE bands indicated that the tested bacteria colonized the endosphere and rhizosphere, and they became an important component of the cultivation-dependent bacteria. The canonical correspondence analysis (CCA) of the DGGE profile and similarity cluster analysis showed that the tested bacteria affected the cultivation-dependent and cultivation-independent bacterial communities in the root endosphere and rhizosphere. In this experiment, the effects and mechanisms of the combined plant-microbe remediation under field conditions were preliminarily studied, and the results are expected to provide a theoretical basis for future combined remediation experiments.

Salt-Tolerant Halophyte Rhizosphere Bacteria Stimulate Growth of Alfalfa in Salty Soil.

Abstract: Halophytes are plants that are adapted to grow in saline soils, and have been widely studied for their physiological and molecular characteristics, but little is known about their associated microbiomes. Bacteria were isolated from the rhizosphere and as root endophytes of Salicornia rubra, Sarcocornia utahensis, and Allenrolfea occidentalis, three native Utah halophytes. A total of 41 independent isolates were identified by 16S rRNA gene sequencing analysis. Isolates were tested for maximum salt tolerance, and some were able to grow in the presence of up to 4 M NaCl. Pigmentation, Gram stain characteristics, optimal temperature for growth, and biofilm formation of each isolate aided in species identification. Some variation in the bacterial population was observed in samples collected at different times of the year, while most of the genera were present regardless of the sampling time. Halomonas, Bacillus, and Kushneria species were consistently isolated both from the soil and as endophytes from roots of all three plant species at all collection times. Non-culturable bacterial species were analyzed by Illumina DNA sequencing. The most commonly identified bacteria were from several phyla commonly found in soil or extreme environments: Acidobacteria, Actinobacteria, Bacteroidetes, Chloroflexi, and Gamma- and Delta-Proteobacteria. Isolates were tested for the ability to stimulate growth of alfalfa under saline conditions. This screening led to the identification of one Halomonas and one Bacillus isolate that, when used to inoculate young alfalfa seedlings, stimulate plant growth in the presence of 1% NaCl, a level that significantly inhibits growth of uninoculated plants. The same bacteria used in the inoculation were recovered from surface sterilized alfalfa roots, indicating the ability of the inoculum to become established as an endophyte. The results with these isolates have exciting promise for enhancing the growth of inoculated alfalfa in salty soil.

Metabolic Basis for Mutualism between Gut Bacteria and Its Impact on the Drosophila melanogaster Host

Abstract: Interactions between species shape the formation and function of microbial communities. In the gut microbiota of animals, cross-feeding of metabolites between microbes can enhance colonization and influence host physiology. We examined a mutually beneficial interaction between two bacteria isolated from the gut microbiota of Drosophila, i.e., Acetobacter fabarum and Lactobacillus brevis. After developing an in vitro coculture assay, we utilized a genetic screen to identify A. fabarum genes required for enhanced growth with L. brevis. The screen, and subsequent genetic analyses, showed that the gene encoding pyruvate phosphate dikinase (ppdK) is required for A. fabarum to benefit fully from coculture. By testing strains with mutations in a range of metabolic genes, we provide evidence that A. fabarum can utilize multiple fermentation products of L. brevis. Mutualism between the bacteria in vivo affects gnotobiotic Drosophila melanogaster; flies associated with A. fabarum and L. brevis showed >1,000-fold increases in bacterial cell density and significantly lower triglyceride storage than monocolonized flies. Mutation of ppdK decreased A. fabarum density in flies cocolonized with L. brevis, consistent with the model in which Acetobacter employs gluconeogenesis to assimilate Lactobacillus fermentation products as a source of carbon in vivo. We propose that cross-feeding between these groups is a common feature of microbiota in Drosophila. IMPORTANCE The digestive tracts of animals are home to a community of microorganisms, the gut microbiota, which affects the growth, development, and health of the host. Interactions among microbes in this inner ecosystem can influence which species colonize the gut and can lead to changes in host physiology. We investigated a mutually beneficial interaction between two bacterial species from the gut microbiota of fruit flies. By coculturing the bacteria in vitro, we were able to identify a metabolic gene required for the bacteria to grow better together than they do separately. Our data suggest that one species consumes the waste products of the other, leading to greater productivity of the microbial community and modifying the nutrients available to the host. This study provides a starting point for investigating how these and other bacteria mutually benefit by sharing metabolites and for determining the impact of mutualism on host health.