Bacterial Invaders Research Articles

Impact of timing on the invasion of synthetic bacterial communities.

Microbial communities regularly experience ecological invasions that can lead to changes in composition and function. Factors thought to impact susceptibility to invasions, such as diversity and resource use, vary over the course of community assembly. We used synthetic bacterial communities to evaluate the success and impact of invasions occurring at different times during the community assembly process. Fifteen distinct communities were subjected to each of three bacterial invaders at the initial assembly of the community ("initial invasion"), 24hours into community assembly ("early invasion"), when the community was still undergoing transient dynamics, and 7days into community assembly ("late invasion"), once the community had settled into its final composition. Communities were passaged daily and characterized through sequencing after reaching a stable composition. Invasions often failed to persist over time, particularly in higher richness communities. However, invasions had their largest effect on composition when they occurred before a community had settled into a stable composition. We found instances where an invader was ultimately excluded yet had profound and long-lasting effects on invaded communities. Invasion outcome was positively associated with lower community richness and resource use efficiency by the community, which varied throughout assembly. Our results demonstrate that microbial communities experiencing transient community dynamics are more affected by, and in some instances prone to, invasion, a finding relevant to efforts to modify the composition of microbial communities.

Streptococcus mutans outer membrane vesicles affect inflammasome activation and the glycolysis of macrophages

Recent studies indicate that bacterial outer membrane vesicles (OMVs) play a significant role in bacterial virulence and pathogenicity. Streptococcus mutans (S. mutans), a principal pathogen in dental caries, secretes a substantial number of OMVs. However, the impact of S. mutans OMVs on oral health and their underlying pathogenic mechanisms remain poorly understood. Macrophages were the initial innate immune cells to respond to bacterial invaders and their products. Therefore, we purified S. mutans OMVs, which stimulated macrophages. Compared to controls, RT-PCR and ELISA analyses revealed that S. mutans OMVs significantly increased the production of IL-1β, IL-6, TNF-α and IL-8, with IL-1β being notably elevated. IL-1β production and secretion are tightly regulated by the inflammasome. Western blot analyses demonstrated that S. mutans OMVs upregulated the expression of inflammasome components, including NLRP3, NLRC4, ASC and AIM2, with a marked increase in NLRP3 expression. Silencing different inflammasome components with siRNA revealed a reduction in IL-1β secretion induced by S. mutans OMVs, particularly through NLRP3. Additionally, ATP production and K+ efflux were found to be crucial for NLRP3 activation. Prolonged stimulation with S. mutans OMVs resulted in increased lactate production and elevated expression of glycolysis-related genes Glut-1, PFKFB3, and HK I, indicating that S. mutans OMVs significantly induce macrophage glycolysis. Furthermore, S. mutans OMVs were shown to enhance biofilm formation, increase S. mutans colonisation on epithelial cells, and inhibit macrophage phagocytosis, thereby improving the survival of S. mutans in the oral cavity. In summary, S. mutans OMVs promote the survival of S. mutans in the mouth through multiple mechanisms, potentially influencing the development of dental caries.

Proresolving Lipid Mediators in the Respiratory System.

Lung inflammation, infection, and injury can lead to critical illness and death. The current means to pharmacologically treat excessive uncontrolled lung inflammation needs improvement because many treatments are or will become immunosuppressive. The inflammatory response evolved to protect the host from microbes, injury, and environmental insults. This response brings phagocytes from the bloodstream to the tissue site to phagocytize and neutralize bacterial invaders and enables airway antimicrobial functions. This physiologic response is ideally self-limited with initiation and resolution phases. Polyunsaturated essential fatty acids are precursors to potent molecules that govern both phases. In the initiation phase, arachidonic acid is converted to prostaglandins and leukotrienes that activate leukocytes to transmigrate from postcapillary venules. The omega-3 fatty acids (e.g., DHA and EPA) are precursors to resolvins, protectins, and maresins, which are families of chemically distinct mediators with potent functions in resolution of acute and chronic inflammation in the respiratory system.

A secreted bacterial protein protects bacteria from cationic antimicrobial peptides by entrapment in phase-separated droplets.

Mammalian hosts combat bacterial infections through the production of defensive cationic antimicrobial peptides (CAPs). These immune factors are capable of directly killing bacterial invaders; however, many pathogens have evolved resistance evasion mechanisms such as cell surface modification, CAP sequestration, degradation, or efflux. We have discovered that several pathogenic and commensal proteobacteria, including the urgent human threat Neisseria gonorrhoeae, secrete a protein (lactoferrin-binding protein B, LbpB) that contains a low-complexity anionic domain capable of inhibiting the antimicrobial activity of host CAPs. This study focuses on a cattle pathogen, Moraxella bovis, that expresses the largest anionic domain of the LbpB homologs. We used an exhaustive biophysical approach employing circular dichroism, biolayer interferometry, cross-linking mass spectrometry, microscopy, size-exclusion chromatography with multi-angle light scattering coupled to small-angle X-ray scattering (SEC-MALS-SAXS), and NMR to understand the mechanisms of LbpB-mediated protection against CAPs. We found that the anionic domain of this LbpB displays an α-helical secondary structure but lacks a rigid tertiary fold. The addition of antimicrobial peptides derived from lactoferrin (i.e. lactoferricin) to the anionic domain of LbpB or full-length LbpB results in the formation of phase-separated droplets of LbpB together with the antimicrobial peptides. The droplets displayed a low rate of diffusion, suggesting that CAPs become trapped inside and are no longer able to kill bacteria. Our data suggest that pathogens, like M. bovis, leverage anionic intrinsically disordered domains for the broad recognition and neutralization of antimicrobials via the formation of biomolecular condensates.

Warmer waters make sturgeon think they're sick

In the lakes and rivers of Manitoba lives the lake sturgeon (Acipenser fulvescens), a large truly prehistoric fish. In years past, this bottom-dwelling fish has been overfished for its meat and eggs, but recent efforts have helped to restore their populations. However, the warming of their waters due to global climate change is causing these sturgeon to face new challenges. Once reaching adulthood, lake sturgeon are hardy and incredibly long lived (the oldest fish caught was estimated to be 125 years old!), but the hatchlings aren't so robust. William Bugg and colleagues from the University of Manitoba, Canada, are trying to determine what happens to the little developing fish when their waters get warmer. Are they in a constant state of stress? And will the warmer waters affect other aspects of their well-being?After obtaining fertilized eggs, the researchers hatched the sturgeon and began the process of getting some of them used to 20°C water. This temperature is within the range that the sturgeon experience in the lakes and rivers early in their development, but these higher temperatures are expected to last longer and get even hotter as the climate changes. The team then measured the expression levels of genes related to stress, including those that are important in fighting off infections. When the fish were raised at 20°C, they had higher levels of mRNA for genes involved in detecting pathogens (bacteria and viruses), the immune system response (to attack the bacteria and viruses) and the stress response. This suggests that being raised in warmer water causes the fish to be stressed and their immune system to respond similarly to the way it does when the fish are sick.So, if the sturgeon were already responding as if they were stressed and sick, what would happen if they really were under attack by bacteria? To answer this, Bugg and colleagues measured the mRNA levels of these same genes after the sturgeon were given doses of bacteria. The sturgeon raised at 20°C couldn't generate as big of a response to these bacterial invaders as sturgeon that were raised at 16°C. This means that sturgeon from warmer waters couldn't fight off bacterial infections as well as those raised in cooler waters. In fact, when given the higher dose of bacteria, 100% of the sturgeon raised in 20°C succumbed to the infection, while only 1.3% of the fish raised at 16°C were unable to fight off the same dose of bacteria.This surprising result led the team to question whether there were other aspects of the sturgeon's stress response or development that were affected by being raised at 20°C. The increased temperature also caused an increase in the levels of the stress hormone cortisol, and a decrease in liver size, which is an indication of the amount of energy stores the fish have. Interestingly, the fish raised at 20°C were bigger, suggesting the sturgeon were putting most of their energy towards growth without reserving as much for energy stores. In this case, having additional energy stores may have helped fish fight off bacterial infections.However, being raised at 20°C did have one potential benefit; it increased the temperature at which fish could function. As the researchers slowly increased the water temperature, they tested the ability of the sturgeon to withstand rising temperatures in the future. Sturgeon raised in warmer waters were able to tolerate hotter water temperatures than those raised at 16°C. So, while our efforts at conserving this important fish species have shown some success, global climate change will present a new and unexpected challenge to these potentially long-lived fish.

Discovery of phage determinants that confer sensitivity to bacterial immune systems

Over the past few years, numerous anti-phage defense systems have been discovered in bacteria. Although the mechanism of defense for some of these systems is understood, a major unanswered question is how these systems sense phage infection. To systematically address this question, we isolated 177 phage mutants that escape 15 different defense systems. In many cases, these escaper phages were mutated in the gene sensed by the defense system, enabling us to map the phage determinants that confer sensitivity to bacterial immunity. Our data identify specificity determinants of diverse retron systems and reveal phage-encodedtriggers for multiple abortive infection systems. We find general themes in phage sensing and demonstrate that mechanistically diverse systems have converged to sense either the core replication machinery of the phage, phage structural components, or host takeover mechanisms. Combining our data with previous findings, we formulate key principles on how bacterial immune systems sense phage invaders.

Experimental Evidence for Manure-Borne Bacteria Invasion in Soil During a Coalescent Event: Influence of the Antibiotic Sulfamethazine

The fertilization of agricultural soil by organic amendment that may contain antibiotics, like manure, can transfer bacterial pathogens and antibiotic-resistant bacteria to soil communities. However, the invasion by manure-borne bacteria in amended soil remains poorly understood. We hypothesized that this kind of process is both influenced by the soil properties (and those of its microbial communities) and by the presence of contaminants such as antibiotics used in veterinary care. To test that, we performed a microcosm experiment in which four different soils were amended or not with manure at an agronomical dose and exposed or not to the antibiotic sulfamethazine (SMZ). After 1 month of incubation, the diversity, structure, and composition of bacterial communities of the soils were assessed by 16S rDNA sequencing. The invasion of manure-borne bacteria was still perceptible 1 month after the soil amendment. The results obtained with the soil already amended in situ with manure 6 months prior to the experiment suggest that some of the bacterial invaders were established in the community over the long term. Even if differences were observed between soils, the invasion was mainly attributable to some of the most abundant OTUs of manure (mainly Firmicutes). SMZ exposure had a limited influence on soil microorganisms but our results suggest that this kind of contaminant can enhance the invasion ability of some manure-borne invaders.

The antimicrobial activity of zinc against group B Streptococcus is strain-dependent across diverse sequence types, capsular serotypes, and invasive versus colonizing isolates

BackgroundStreptococcus agalactiae or Group B Streptococcus (GBS) is an encapsulated gram-positive bacterial pathobiont that commonly colonizes the lower gastrointestinal tract and reproductive tract of human hosts. This bacterium can infect the gravid reproductive tract and cause invasive infections of pregnant patients and neonates. Upon colonizing the reproductive tract, the bacterial cell is presented with numerous nutritional challenges imposed by the host. One strategy employed by the host innate immune system is intoxication of bacterial invaders with certain transition metals such as zinc.MethodologyPrevious work has demonstrated that GBS must employ elegant strategies to circumnavigate zinc stress in order to survive in the vertebrate host. We assessed 30 strains of GBS from diverse isolation sources, capsular serotypes, and sequence types for susceptibility or resistance to zinc intoxication.ResultsInvasive strains, such as those isolated from early onset disease manifestations of GBS infection were significantly less susceptible to zinc toxicity than colonizing strains isolated from rectovaginal swabs of pregnant patients. Additionally, capsular type III (cpsIII) strains and the ST-17 and ST-19 strains exhibited the greatest resilience to zinc stress, whereas ST-1 and ST-12 strains as well as those possessing capsular type Ib (cpsIb) were more sensitive to zinc intoxication. Thus, this study demonstrates that the transition metal zinc possesses antimicrobial properties against a wide range of GBS strains, with isolation source, capsular serotype, and sequence type contributing to susceptibility or resistance to zinc stress.

Manipulation of phyllosphere bacterial communities reversibly alters the plant microbiome and leaf traits in the field

Bacterial communities in the phyllosphere are shaped by host genotype and phenotype and spatio-temporal variation of the environment. In turn, bacteria have the potential for altering the plant phenotype. Field experiments can help to estimate bacterial effects on plant functional traits under natural conditions. We used a transplantation approach of culturable bacterial communities to explore how manipulation of leaf-associated microbial communities in two different successional stages within a glacier foreland can influence microbial composition and functional plant traits. Our study documents successional stage-specific variations in the composition of foliar bacterial communities and shifts therein throughout a season and between years. We show that cultured bacteria transferred between plant communities can alter diversity and composition of the microbiome on plant community level as well as species-specific functional plant traits of two selected plant species within one growing season. Furthermore, our results demonstrate a strong resilience of plant-associated bacterial communities and of plants in response to bacterial invaders. Our study illustrates that inoculation experiments in the field with naturally occurring microbial communities of wild plants are suited to investigate complex interactions between microbial communities, the environment, and plant traits.

Bacterial lipids earmarked with ubiquitin for pathogen clearance

As a component of cell-autonomous immunity, cytosolic bacterial invaders are earmarked with the protein modifier ubiquitin for targeted xenophagic destruction. Otten etal. (2021) reveal that unique bacterial lipids are unconventional sites for ubiquitination and initiate downstream pathogen clearance.

Temperate Bacteriophages-The Powerful Indirect Modulators of Eukaryotic Cells and Immune Functions.

Bacteriophages are natural biological entities that limit the growth and amplification of bacteria. They are important stimulators of evolutionary variability in bacteria, and currently are considered a weapon against antibiotic resistance of bacteria. Nevertheless, apart from their antibacterial activity, phages may act as modulators of mammalian immune responses. In this paper, we focus on temperate phages able to execute the lysogenic development, which may shape animal or human immune response by influencing various processes, including phagocytosis of bacterial invaders and immune modulation of mammalian host cells.

Roles of Eicosanoids in Regulating Inflammation and Neutrophil Migration as an Innate Host Response to Bacterial Infections.

Eicosanoids are lipid-based signaling molecules that play a unique role in innate immune responses. The multiple types of eicosanoids, such as prostaglandins (PGs) and leukotrienes (LTs), allow the innate immune cells to respond rapidly to bacterial invaders. Bacterial pathogens alter cyclooxygenase (COX)-derived prostaglandins (PGs) in macrophages, such as PGE2 15d-PGJ2, and lipoxygenase (LOX)-derived leukotriene LTB4, which has chemotactic functions. The PG synthesis and secretion are regulated by substrate availability of arachidonic acid and by the COX-2 enzyme, and the expression of this protein is regulated at multiple levels, both transcriptionally and posttranscriptionally. Bacterial pathogens use virulence strategies such as type three secretion systems (T3SSs) to deliver virulence factors altering the expression of eicosanoid-specific biosynthetic enzymes, thereby modulating the host response to bacterial lipopolysaccharides (LPS). Recent advances have identified a novel role of eicosanoids in inflammasome activation during intracellular infection with bacterial pathogens. Specifically, PGE2 was found to enhance inflammasome activation, driving the formation of pore-induced intracellular traps (PITs), thus trapping bacteria from escaping the dying cell. Finally, eicosanoids and IL-1β released from macrophages are implicated in the efferocytosis of neighboring neutrophils. Neutrophils play an essential role in phagocytosing and degrading PITs and associated bacteria to restore homeostasis. This review focuses on the novel functions of host-derived eicosanoids in the host-pathogen interactions.

Molecular characterization of a novel p38 MAPK cDNA from Cyclina sinensis and its potential immune-related function under the threat of Vibrio anguillarum

The p38 mitogen-activated protein kinase (MAPK) is one important member of MAPK family and reported to serve a predominant function in regulating innate immunity after the occurrence of certain infection. In the present study, one novel p38 MAPK gene was acquired from Cyclina sinensis based on the RNA-seq analysis and designated as Csp38 MAPK. This novel gene contained a full length of 1781bp, 1104bp of which was deemed as open reading frames and gave rise to a peptide of 367 amino acids with a predicted molecular weight of 42.31 KDa. A conserved serine/threonine protein kinase (S_Tkc) region along with a Thr-Gly-Tyr motif was discovered in the deduced sequence. According to the phylogenetic analysis, there was a close relationship between this kinase and Meretrix petechialis p38 MAPK. As for the expression pattern, this newly-identified Csp38 MAPK was ubiquitously distributed in several tissues throughout the body but with varied abundance. After the challenge of Vibrio anguillarum, both the transcription and phosphorylation level of Csp38 MAPK in hemolymph were coordinately altered with a time-dependent manner. Besides, with the application of double strand RNA homologous to myeloid differentiation factor 88 (MyD88) of C. sinensis, the activation of Csp38 MAPK was found to obviously decrease in hemolymph after the pathogen stimulation. Hence, our experimental data presented evidence for the potential involvement of p38 MAPK in response to bacterial invaders in C. sinensis, possibly facilitating the understanding for pathogen-induced innate immunity in clams.

Evolution of the guanylate binding protein (GBP) genes: Emergence of GBP7 genes in primates and further acquisition of a unique GBP3 gene in simians

Guanylate binding proteins (GBPs) are major players in the host immunity, providing defense against bacterial and viral invaders. Multigene families may suffer different processes of evolution. Gene families related to the immune system usually follow the birth-and-death evolution process, where duplicated genes can be deleted, gain new functions or become non-functional. We analyzed publicly available primate GBP sequences and their genomic organization and observed that GBP7 genes appear to have emerged from a duplication of GBP4 and seem to be only present in primates. Furthermore, GBP3 genes are only present in Simiiformes and probably originated from GBP1 genes. Finally, a duplication event occurred in the GBP6 in Tarsiiformes and became functional which might also explain the duplication of GBP6 in New World monkeys and Cercopithecidae. Taken together, this study provides new knowledge on the evolution of GBPs in primates and suggests that a revision of the GBPs nomenclature is necessary.

Genomic Profiling Reveals Distinct Routes To Complement Resistance in Klebsiella pneumoniae.

The serum complement system is a first line of defense against bacterial invaders. Resistance to killing by serum enhances the capacity of Klebsiella pneumoniae to cause infection, but it is an incompletely understood virulence trait. Identifying and characterizing the factors responsible for preventing activation of, and killing by, serum complement could inform new approaches to treatment of K. pneumoniae infections. Here, we used functional genomic profiling to define the genetic basis of complement resistance in four diverse serum-resistant K. pneumoniae strains (NTUH-K2044, B5055, ATCC 43816, and RH201207), and explored their recognition by key complement components. More than 90 genes contributed to resistance in one or more strains, but only three, rfaH, lpp, and arnD, were common to all four strains. Deletion of the antiterminator rfaH, which controls the expression of capsule and O side chains, resulted in dramatic complement resistance reductions in all strains. The murein lipoprotein gene lpp promoted capsule retention through a mechanism dependent on its C-terminal lysine residue; its deletion led to modest reductions in complement resistance. Binding experiments with the complement components C3b and C5b-9 showed that the underlying mechanism of evasion varied in the four strains: B5055 and NTUH-K2044 appeared to bypass recognition by complement entirely, while ATCC 43816 and RH201207 were able to resist killing despite being associated with substantial levels of C5b-9. All rfaH and lpp mutants bound C3b and C5b-9 in large quantities. Our findings show that, even among this small selection of isolates, K. pneumoniae adopts differing mechanisms and utilizes distinct gene sets to avoid complement attack.

Transbilayer Movement of Sphingomyelin Precedes Catastrophic Breakage of Enterobacteria-Containing Vacuoles

SummaryPathogenic bacteria enter the cytosol of host cells through uptake into bacteria-containing vacuoles (BCVs) and subsequent rupture of the vacuolar membrane [1]. Bacterial invaders are sensed either directly, through cytosolic pattern-recognition receptors specific for bacterial ligands, or indirectly, through danger receptors that bind host molecules displayed in an abnormal context, for example, glycans on damaged BCVs [2, 3, 4]. In contrast to damage caused by Listeria monocytogenes, a Gram-positive bacterium, BCV rupture by Gram-negative pathogens such as Shigella flexneri or Salmonella Typhimurium remains incompletely understood [5, 6]. The latter may cause membrane damage directly, when inserting their Type Three Secretion needles into host membranes, or indirectly through translocated bacterial effector proteins [7, 8, 9]. Here, we report that sphingomyelin, an abundant lipid of the luminal leaflet of BCV membranes, and normally absent from the cytosol, becomes exposed to the cytosol as an early predictive marker of BCV rupture by Gram-negative bacteria. To monitor subcellular sphingomyelin distribution, we generated a live sphingomyelin reporter from Lysenin, a sphingomyelin-specific toxin from the earthworm Eisenia fetida [10, 11]. Using super resolution live imaging and correlative light and electron microscopy (CLEM), we discovered that BCV rupture proceeds through two distinct successive stages: first, sphingomyelin is gradually translocated into the cytosolic leaflet of the BCV, invariably followed by cytosolic exposure of glycans, which recruit galectin-8, indicating bacterial entry into the cytosol. Exposure of sphingomyelin on BCVs may therefore act as an early danger signal alerting the cell to imminent bacterial invasion.

Combined Prebiotic and Microbial Intervention Improves Oral Cholera Vaccination Responses in a Mouse Model of Childhood Undernutrition

Undernourished children in low-income countries often exhibit poor responses to oral vaccination. Perturbed microbiota development is linked to undernutrition, but whether and how microbiota changes affect vaccine responsiveness remains unclear. Here, we show that gnotobiotic mice colonized with microbiota from undernourished Bangladeshi children and fed a Bangladeshi diet exhibited microbiota-dependent differences in mucosal IgA responses to oral vaccination with cholera toxin (CT). Supplementation with a nutraceutical consisting of spirulina, amaranth, flaxseed, and micronutrients augmented CT-IgA production. Mice initially colonized with a microbiota associated with poor CT responses exhibited improved immunogenicity upon invasion of bacterial taxa from cagemates colonized with a more "responsive" microbiota. Additionally, a consortium of five cultured bacterial invaders conferred augmented CT-IgA responses in mice fed the supplemented diet and colonized with the "hypo-responsive" community. These results provide preclinical proof-of-concept that diet and microbiota influence mucosal immune responses to CT vaccination and identify a candidate synbiotic formulation.

Iron Acquisition by Bacterial Pathogens: Beyond Tris-Catecholate Complexes.

Sequestration of the essential nutrient iron from bacterial invaders that colonize the vertebrate host is a central feature of nutritional immunity and the "fight over transition metals" at the host-pathogen interface. The iron quota for many bacterial pathogens is large, as iron enzymes often make up a significant share of the metalloproteome. Iron enzymes play critical roles in respiration, energy metabolism, and other cellular processes by catalyzing a wide range of oxidation-reduction, electron transfer, and oxygen activation reactions. In this Concept article, we discuss recent insights into the diverse ways that bacterial pathogens acquire this essential nutrient, beyond the well-characterized tris-catecholate FeIII complexes, in competition and cooperation with significant host efforts to cripple these processes. We also discuss pathogen strategies to adapt their metabolism to less-than-optimal iron concentrations, and briefly speculate on what might be an integrated adaptive response to the concurrent limitation of both iron and zinc in the infected host.

Granzyme B Attenuates Bacterial Virulence by Targeting Secreted Factors.

SummaryPathogenic bacteria secrete virulence factors that interact with the human host to establish infections. The human immune system evolved multiple mechanisms to fight bacterial invaders, including immune proteases that were demonstrated to contribute crucially to antibacterial defense. Here we show that granzyme B degrades multiple secreted virulence mediators from Listeria monocytogenes, Salmonella typhimurium, and Mycobacteria tuberculosis. Pathogenic bacteria, when infected in the presence of granzyme B or granzyme-secreting killer cells, fail to grow in human macrophages and epithelial cells owing to their crippled virulence. A granzyme B-uncleavable mutant form of the major Listeria virulence factor, listeriolysin O, rescued the virulence defect in response to granzyme treatment. Hence, we link the degradation of a single factor with the observed decrease in virulent bacteria growth. Overall, we reveal here an innate immune barrier function of granzyme B by disrupting bacterial virulence to facilitate bacteria clearance by bystander immune and non-immune cells.

Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense.

Macrophage-mediated phagocytosis and cytokine production represent the front lines of resistance to bacterial invaders. A key feature of this pro-inflammatory response in mammals is the complex remodeling of cellular metabolism towards aerobic glycolysis. Although the function of bactericidal macrophages is highly conserved, the metabolic remodeling of insect macrophages remains poorly understood. Here, we used adults of the fruit fly Drosophila melanogaster to investigate the metabolic changes that occur in macrophages during the acute and resolution phases of Streptococcus-induced sepsis. Our studies revealed that orthologs of Hypoxia inducible factor 1α (HIF1α) and Lactate dehydrogenase (LDH) are required for macrophage activation, their bactericidal function, and resistance to infection, thus documenting the conservation of this cellular response between insects and mammals. Further, we show that macrophages employing aerobic glycolysis induce changes in systemic metabolism that are necessary to meet the biosynthetic and energetic demands of their function and resistance to bacterial infection.