Functional Redundancy in the Hydroxycinnamate Catabolism Pathways of the Salt Marsh BacteriumSagittula stellataE-37

ABSTRACTThe hydroxycinnamates (HCAs) ferulate andp-coumarate are among the most abundant constituents of lignin, and their degradation by bacteria is an essential step in the remineralization of vascular plant material. Here, we investigate the catabolism of these two HCAs by the marine bacteriumSagittula stellataE-37, a member of the roseobacter lineage with lignolytic potential. Bacterial degradation of HCAs is often initiated by the activity of a hydroxycinnamoyl-coenzyme A (hydroxycinnamoyl-CoA) synthase. Genome analysis ofS. stellatarevealed the presence of two feruloyl-CoA (fcs) synthase homologs, an unusual occurrence among characterized HCA degraders. In order to elucidate the role of these homologs in HCA catabolism,fcs-1andfcs-2were disrupted using insertional mutagenesis, yielding both single and doublefcsmutants. Growth onp-coumarate was abolished in thefcsdouble mutant, whereas maximum cell yield on ferulate was only 2% of that of the wild type. Interestingly, the single mutants demonstrated opposing phenotypes, where thefcs-1mutant showed impaired growth (extended lag and ∼60% of wild-type rate) onp-coumarate, and thefcs-2mutant showed impaired growth (extended lag and ∼20% of wild-type rate) on ferulate, pointing to distinct but overlapping roles of the encodedfcshomologs, withfcs-1primarily dedicated top-coumarate utilization andfcs-2playing a dominant role in ferulate utilization. Finally, a tripartite ATP-independent periplasmic (TRAP) family transporter was found to be required for growth on both HCAs. These findings provide evidence for functional redundancy in the degradation of HCAs inS. stellataE-37 and offer important insight into the genetic complexity of aromatic compound degradation in bacteria.IMPORTANCEHydroxycinnamates (HCAs) are essential components of lignin and are involved in various plant functions, including defense. In nature, microbial degradation of HCAs is influential to global carbon cycling. HCA degradation pathways are also of industrial relevance, as microbial transformation of the HCA, ferulate, can generate vanillin, a valuable flavoring compound. Yet, surprisingly little is known of the genetics underlying bacterial HCA degradation. Here, we make comparisons to previously characterized bacterial HCA degraders and use a genetic approach to characterize genes involved in catabolism and uptake of HCAs in the environmentally relevant marine bacteriumSagittula stellata. We provide evidence of overlapping substrate specificity between HCA degradation pathways and uptake proteins. We conclude thatS. stellatais uniquely poised to utilize HCAs found in the complex mixtures of plant-derived compounds in nature. This strategy may be common among marine bacteria residing in lignin-rich coastal waters and has potential relevance to biotechnology sectors.

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White Mutants of Chloroperoxidase-Secreting Caldariomyces fumago as Superior Production Strains, Revealing an Interaction between Pigmentation and Enzyme Secretion

Applied and Environmental Microbiology ◽

10.1128/aem.00570-12 ◽

2012 ◽

Vol 78 (16) ◽

pp. 5923-5925 ◽

Cited By ~ 3

Author(s):

Markus Buchhaupt ◽

Sonja Hüttmann ◽

Jens Schrader

Keyword(s):

Culture Supernatant ◽

Downstream Processing ◽

Enzyme Secretion ◽

Wild Type ◽

Content Type ◽

Caldariomyces Fumago ◽

Dark Pigment ◽

Type Rate ◽

Wild Type Rate

ABSTRACTBy mutant-colony screening ofCaldariomyces fumago, several white mutants were isolated that are superior strains for the production of the valuable enzyme chloroperoxidase (CPO). Their culture supernatant lacks the contaminating dark pigment, which simplifies downstream processing. Furthermore, the CPO content increased significantly faster than the wild-type rate, which uncovers possible interactions between pigmentation and enzyme secretion.

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ESCAPE FROM MATING-TYPE INCOMPATIBILITY IN BISEXUAL (A + a) NEUROSPORA HETEROKARYONS

Canadian Journal of Genetics and Cytology ◽

10.1139/g75-058 ◽

1975 ◽

Vol 17 (3) ◽

pp. 441-449 ◽

Cited By ~ 11

Author(s):

A. M. DeLange ◽

A. J. F. Griffiths

Keyword(s):

Mating Type ◽

Loss Of Function ◽

Wild Type ◽

Opposite Mating Type ◽

Type Locus ◽

Heterokaryon Incompatibility ◽

Recessive Mutant ◽

Type Rate ◽

Wild Type Rate ◽

Incompatibility Locus

In Neurospora crassa, strains of opposite mating type generally do not form stable heterokaryons because the mating type locus acts as a heterokaryon incompatibility locus. However, when one A and one a strain, having complementing auxotrophic mutants, are placed together on minimal medium, growth may occur, although the growth is generally slow. In this study, escape from such slow growth to that at a wild type or near-wild type rate was observed. The escaped cultures are stable heterokaryons, mostly having lost the mating type allele function from one component nucleus, so that the nuclear types are heterokaryon compatible. Either A or a mating type can be lost. This loss of function has been attributed to deletion since only one nuclear type could be recovered in all heterokaryons except one, but deletion spanning adjacent loci has been directly demonstrated in a minority of cases. Alternatively when one component strain is tol and the other tol+ (tol being a recessive mutant suppressing the heterokaryon incompatibility associated with mating type), escape may occur by the deletion or mutation of tol+, also resulting in heterokaryon compatibility. An induction mechanism for escape is speculated upon.

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The Pseudomonas aeruginosa devB/SOL Homolog,pgl, Is a Member of the hex Regulon and Encodes 6-Phosphogluconolactonase

Journal of Bacteriology ◽

10.1128/jb.182.14.3934-3941.2000 ◽

2000 ◽

Vol 182 (14) ◽

pp. 3934-3941 ◽

Cited By ~ 24

Author(s):

Paul W. Hager ◽

M. Worth Calfee ◽

Paul V. Phibbs

Keyword(s):

Pseudomonas Aeruginosa ◽

Carbon Source ◽

Normal Growth ◽

Wild Type ◽

Reading Frame ◽

Cell Extracts ◽

Genes Encoding ◽

Type Rate ◽

Glucose 6 Phosphate Dehydrogenase ◽

Wild Type Rate

ABSTRACT A cyclic version of the Entner-Doudoroff pathway is used byPseudomonas aeruginosa to metabolize carbohydrates. Genes encoding the enzymes that catabolize intracellular glucose to pyruvate and glyceraldehyde 3-phosphate are coordinately regulated, clustered at 39 min on the chromosome, and collectively form thehex regulon. Within the hex cluster is an open reading frame (ORF) with homology to the devB/SOLfamily of unidentified proteins. This ORF encodes a protein of either 243 or 238 amino acids; it overlaps the 5′ end of zwf (encodes glucose-6-phosphate dehydrogenase) and is followed immediately by eda (encodes the Entner-Doudoroff aldolase). The devB/SOL homolog was inactivated in P. aeruginosa PAO1 by recombination with a suicide plasmid containing an interrupted copy of the gene, creating mutant strain PAO8029. PAO8029 grows at 9% of the wild-type rate using mannitol as the carbon source and at 50% of the wild-type rate using gluconate as the carbon source. Cell extracts of PAO8029 were specifically deficient in 6-phosphogluconolactonase (Pgl) activity. The cloned devB/SOL homolog complemented PAO8029 to restore normal growth on mannitol and gluconate and restored Pgl activity. Hence, we have identified this gene as pgland propose that the devB/SOL family members encode 6-phosphogluconolactonases. Interestingly, three eukaryotic glucose-6-phosphate dehydrogenase (G6PDH) isozymes, from human, rabbit, and Plasmodium falciparum, contain Pgl domains, suggesting that the sequential reactions of G6PDH and Pgl are incorporated in a single protein. 6-Phosphogluconolactonase activity is induced in P. aeruginosa PAO1 by growth on mannitol and repressed by growth on succinate, and it is expressed constitutively in P. aeruginosa PAO8026 (hexR). Taken together, these results establish that Pgl is an essential enzyme of the cyclic Entner-Doudoroff pathway encoded by pgl, a structural gene of the hex regulon.

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MrkD1Pfrom Klebsiella pneumoniae Strain IA565 Allows for Coexistence with Pseudomonas aeruginosa and Protection from Protease-Mediated Biofilm Detachment

Infection and Immunity ◽

10.1128/iai.00521-13 ◽

2013 ◽

Vol 81 (11) ◽

pp. 4112-4120 ◽

Cited By ~ 11

Author(s):

Brandon M. Childers ◽

Tricia A. Van Laar ◽

Tao You ◽

Steven Clegg ◽

Kai P. Leung

Keyword(s):

Pseudomonas Aeruginosa ◽

Klebsiella Pneumoniae ◽

Chronic Wounds ◽

Chronic Wound ◽

Single Species ◽

Wild Type ◽

Content Type ◽

Biofilm Model ◽

Essential Components

ABSTRACTBiofilm formation and persistence are essential components for the continued survival of pathogens inside the host and constitute a major contributor to the development of chronic wounds with resistance to antimicrobial compounds. Understanding these processes is crucial for control of biofilm-mediated disease. Though chronic wound infections are often polymicrobial in nature, much of the research on chronic wound-related microbes has focused on single-species models.Klebsiella pneumoniaeandPseudomonas aeruginosaare microbes that are often found together in wound isolates and are able to form stablein vitrobiofilms, despite the antagonistic nature ofP. aeruginosawith other organisms. Mutants of theK. pneumoniaestrain IA565 lacking the plasmid-bornemrkD1Pgene were less competitive than the wild type in anin vitrodual-species biofilm model withP. aeruginosa(PAO1). PAO1 spent medium inhibited the formation of biofilm ofmrkD1P-deficient mutants and disrupted preestablished biofilms, with no effect on IA565 and no effect on the growth of the wild type or mutants. A screen using a two-allele PAO1 transposon library identified the LasB elastase as the secreted effector involved in biofilm disruption, and a purified version of the protein produced results similar to those with PAO1 spent medium. Various other proteases had a similar effect, suggesting that the disruption of themrkD1Pgene causes sensitivity to general proteolytic effects and indicating a role for MrkD1Pin protection against host antibiofilm effectors. Our results suggest that MrkD1Pallows for competition ofK. pneumoniaewithP. aeruginosain a mixed-species biofilm and provides defense against microbial and host-derived proteases.

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Generation of a Prophage-Free Variant of the Fast-Growing BacteriumVibrio natriegens

Applied and Environmental Microbiology ◽

10.1128/aem.00853-19 ◽

2019 ◽

Vol 85 (17) ◽

Cited By ~ 4

Author(s):

Eugen Pfeifer ◽

Slawomir Michniewski ◽

Cornelia Gätgens ◽

Eugenia Münch ◽

Felix Müller ◽

...

Keyword(s):

Molecular Biology ◽

Marine Bacterium ◽

Phenotypic Characterization ◽

Competitive Growth ◽

Growth Experiment ◽

Wild Type ◽

Cultivation Conditions ◽

Content Type ◽

Fast Growing ◽

Free Strain

ABSTRACTThe fast-growing marine bacteriumVibrio natriegensrepresents an emerging strain for molecular biology and biotechnology. Genome sequencing and quantitative PCR analysis revealed that the first chromosome ofV. natriegensATCC 14048 contains two prophage regions (VNP1 and VNP2) that are both inducible by the DNA-damaging agent mitomycin C and exhibit spontaneous activation under standard cultivation conditions. Their activation was also confirmed by live cell imaging of an mCherry fusion to the major capsid proteins of VNP1 and VNP2. Transmission electron microscopy visualized the release of phage particles belonging to theSiphoviridaefamily into the culture supernatant. FreeingV. natriegensfrom its proviral load, followed by phenotypic characterization, revealed an improved robustness of the prophage-free variant toward DNA-damaging conditions, reduced cell lysis under hypo-osmotic conditions, and an increased pyruvate production compared to wild-type levels. Remarkably, the prophage-free strain outcompeted the wild type in a competitive growth experiment, emphasizing that this strain is a promising platform for future metabolic engineering approaches.IMPORTANCEThe fast-growing marine bacteriumVibrio natriegensrepresents an emerging model host for molecular biology and biotechnology, featuring a reported doubling time of less than 10 minutes. In many bacterial species, viral DNA (prophage elements) may constitute a considerable fraction of the whole genome and may have detrimental effects on the growth and fitness of industrial strains. Genome analysis revealed the presence of two prophage regions in theV. natriegensgenome that were shown to undergo spontaneous induction under standard cultivation conditions. In this study, we generated a prophage-free variant ofV. natriegens. Remarkably, the prophage-free strain exhibited a higher tolerance toward DNA damage and hypo-osmotic stress. Moreover, it was shown to outcompete the wild-type strain in a competitive growth experiment. In conclusion, our study presents the prophage-free variant ofV. natriegensas a promising platform strain for future biotechnological applications.

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Interspecies Electron Transfer via Hydrogen and Formate Rather than Direct Electrical Connections in Cocultures of Pelobacter carbinolicus and Geobacter sulfurreducens

Applied and Environmental Microbiology ◽

10.1128/aem.01946-12 ◽

2012 ◽

Vol 78 (21) ◽

pp. 7645-7651 ◽

Cited By ~ 87

Author(s):

Amelia-Elena Rotaru ◽

Pravin M. Shrestha ◽

Fanghua Liu ◽

Toshiyuki Ueki ◽

Kelly Nevin ◽

...

Keyword(s):

Electron Transfer ◽

Formate Dehydrogenase ◽

Geobacter Sulfurreducens ◽

Close Relative ◽

Wild Type ◽

Geobacter Metallireducens ◽

Content Type ◽

Interspecies Electron Transfer ◽

Essential Components ◽

Electrical Connections

ABSTRACTDirect interspecies electron transfer (DIET) is an alternative to interspecies H2/formate transfer as a mechanism for microbial species to cooperatively exchange electrons during syntrophic metabolism. To understand what specific properties contribute to DIET, studies were conducted withPelobacter carbinolicus, a close relative ofGeobacter metallireducens, which is capable of DIET.P. carbinolicusgrew in coculture withGeobacter sulfurreducenswith ethanol as the electron donor and fumarate as the electron acceptor, conditions under whichG. sulfurreducensformed direct electrical connections withG. metallireducens. In contrast to the cell aggregation associated with DIET,P. carbinolicusandG. sulfurreducensdid not aggregate. Attempts to initiate cocultures with a genetically modified strain ofG. sulfurreducensincapable of both H2and formate utilization were unsuccessful, whereas cocultures readily grew with mutant strains capable of formate but not H2uptake or vice versa. The hydrogenase mutant ofG. sulfurreducenscompensated, in cocultures, with significantly increased formate dehydrogenase gene expression. In contrast, the transcript abundance of a hydrogenase gene was comparable in cocultures with that for the formate dehydrogenase mutant ofG. sulfurreducensor the wild type, suggesting that H2was the primary electron carrier in the wild-type cocultures. Cocultures were also initiated with strains ofG. sulfurreducensthat could not produce pili or OmcS, two essential components for DIET. The finding thatP. carbinolicusexchanged electrons withG. sulfurreducensvia interspecies transfer of H2/formate rather than DIET demonstrates that not all microorganisms that can grow syntrophically are capable of DIET and that closely related microorganisms may use significantly different strategies for interspecies electron exchange.

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Prevalence and Antifungal Susceptibility of Candida parapsilosis Species Complex in Eastern China: A 15-Year Retrospective Study by ECIFIG

Frontiers in Microbiology ◽

10.3389/fmicb.2021.644000 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jian Guo ◽

Min Zhang ◽

Dan Qiao ◽

Hui Shen ◽

Lili Wang ◽

...

Keyword(s):

Species Complex ◽

Candida Parapsilosis ◽

Geometric Mean ◽

Eastern China ◽

Antifungal Susceptibility ◽

Alternative Therapy ◽

Wild Type ◽

Type Rate ◽

Candida Orthopsilosis ◽

Wild Type Rate

Candida parapsilosis complex is one of the most common non-albicans Candida species that cause candidemia, especially invasive candidiasis. The purpose of this study was to evaluate the antifungal susceptibilities of both colonized and invasive clinical C. parapsilosis complex isolates to 10 drugs: amphotericin (AMB), anidulafungin (AFG), caspofungin (CAS), micafungin (MFG), fluconazole (FLZ), voriconazole (VRZ), itraconazole (ITZ), posaconazole (POZ), 5-flucytosine (FCY), and isaconazole (ISA). In total, 884 C. parapsilosis species complex isolates were gathered between January 2005 and December 2020. C. parapsilosis, Candida metapsilosis, and Candida orthopsilosis accounted for 86.3, 8.1, and 5.5% of the cryptic species, respectively. The resistance/non-wild-type rate of bloodstream C. parapsilosis to the drugs was 3.5%, of C. metapsilosis to AFG and CAS was 7.7%, and of C. orthopsilosis to FLZ and VRZ was 15% and to CAS, MFG, and POZ was 5%. The geometric mean (GM) minimum inhibitory concentrations (MICs) of non-bloodstream C. parapsilosis for CAS (0.555 mg/L), MFG (0.853 mg/L), FLZ (0.816 mg/L), VRZ (0.017 mg/L), ITZ (0.076 mg/L), and POZ (0.042 mg/L) were significantly higher than those of bloodstream C. parapsilosis, for which the GM MICs were 0.464, 0.745, 0.704, 0.015, 0.061, and 0.033 mg/L, respectively (P < 0.05). The MIC distribution of the bloodstream C. parapsilosis strains collected from 2019 to 2020 for VRZ, POZ, and ITZ were 0.018, 0.040, and 0.073 mg/L, significantly higher than those from 2005 to 2018, which were 0.013, 0.028, and 0.052 mg/L (P < 0.05). Additionally, MIC distributions of C. parapsilosis with FLZ and the distributions of C. orthopsilosis with ITZ and POZ might be higher than those in Clinical and Laboratory Standards Institute studies. Furthermore, a total of 143 C. parapsilosis complex isolates showed great susceptibility to ISA. Overall, antifungal treatment of the non-bloodstream C. parapsilosis complex isolates should be managed and improved. The clinicians are suggested to pay more attention on azoles usage for the C. parapsilosis complex isolates. In addition, establishing the epidemiological cutoff values (ECVs) for azoles used in Eastern China may offer better guidance for clinical treatments. Although ISA acts on the same target as other azoles, it may be used as an alternative therapy for cases caused by FLZ- or VRZ-resistant C. parapsilosis complex strains.

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Pyruvate Is Synthesized by Two Pathways in Pea Bacteroids with Different Efficiencies for Nitrogen Fixation

Journal of Bacteriology ◽

10.1128/jb.00294-10 ◽

2010 ◽

Vol 192 (19) ◽

pp. 4944-4953 ◽

Cited By ~ 14

Author(s):

Geraldine Mulley ◽

Miguel Lopez-Gomez ◽

Ye Zhang ◽

Jason Terpolilli ◽

Jurgen Prell ◽

...

Keyword(s):

Nitrogen Fixation ◽

Malic Enzyme ◽

Rhizobium Leguminosarum ◽

Reduction Rate ◽

Dicarboxylic Acids ◽

Dry Weight ◽

Wild Type ◽

Type Rate ◽

Pep Carboxykinase ◽

Wild Type Rate

ABSTRACT Nitrogen fixation in legume bacteroids is energized by the metabolism of dicarboxylic acids, which requires their oxidation to both oxaloacetate and pyruvate. In alfalfa bacteroids, production of pyruvate requires NAD+ malic enzyme (Dme) but not NADP+ malic enzyme (Tme). However, we show that Rhizobium leguminosarum has two pathways for pyruvate formation from dicarboxylates catalyzed by Dme and by the combined activities of phosphoenolpyruvate (PEP) carboxykinase (PckA) and pyruvate kinase (PykA). Both pathways enable N2 fixation, but the PckA/PykA pathway supports N2 fixation at only 60% of that for Dme. Double mutants of dme and pckA/pykA did not fix N2. Furthermore, dme pykA double mutants did not grow on dicarboxylates, showing that they are the only pathways for the production of pyruvate from dicarboxylates normally expressed. PckA is not expressed in alfalfa bacteroids, resulting in an obligate requirement for Dme for pyruvate formation and N2 fixation. When PckA was expressed from a constitutive nptII promoter in alfalfa dme bacteroids, acetylene was reduced at 30% of the wild-type rate, although this level was insufficient to prevent nitrogen starvation. Dme has N-terminal, malic enzyme (Me), and C-terminal phosphotransacetylase (Pta) domains. Deleting the Pta domain increased the peak acetylene reduction rate in 4-week-old pea plants to 140 to 150% of the wild-type rate, and this was accompanied by increased nodule mass. Plants infected with Pta deletion mutants did not have increased dry weight, demonstrating that there is not a sustained change in nitrogen fixation throughout growth. This indicates a complex relationship between pyruvate synthesis in bacteroids, nitrogen fixation, and plant growth.

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Mutations in fbiD (Rv2983) as a Novel Determinant of Resistance to Pretomanid and Delamanid in Mycobacterium tuberculosis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01948-20 ◽

2020 ◽

Vol 65 (1) ◽

pp. e01948-20

Author(s):

Dalin Rifat ◽

Si-Yang Li ◽

Thomas Ioerger ◽

Keshav Shah ◽

Jean-Philippe Lanoix ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Clinical Evidence ◽

Clinical Samples ◽

Loss Of Function ◽

Wild Type ◽

Content Type ◽

Solid Media ◽

High Level ◽

Level Resistance

ABSTRACTThe nitroimidazole prodrugs delamanid and pretomanid comprise one of only two new antimicrobial classes approved to treat tuberculosis (TB) in 50 years. Prior in vitro studies suggest a relatively low barrier to nitroimidazole resistance in Mycobacterium tuberculosis, but clinical evidence is limited to date. We selected pretomanid-resistant M. tuberculosis mutants in two mouse models of TB using a range of pretomanid doses. The frequency of spontaneous resistance was approximately 10−5 CFU. Whole-genome sequencing of 161 resistant isolates from 47 mice revealed 99 unique mutations, of which 91% occurred in 1 of 5 genes previously associated with nitroimidazole activation and resistance, namely, fbiC (56%), fbiA (15%), ddn (12%), fgd (4%), and fbiB (4%). Nearly all mutations were unique to a single mouse and not previously identified. The remaining 9% of resistant mutants harbored mutations in Rv2983 (fbiD), a gene not previously associated with nitroimidazole resistance but recently shown to be a guanylyltransferase necessary for cofactor F420 synthesis. Most mutants exhibited high-level resistance to pretomanid and delamanid, although Rv2983 and fbiB mutants exhibited high-level pretomanid resistance but relatively small changes in delamanid susceptibility. Complementing an Rv2983 mutant with wild-type Rv2983 restored susceptibility to pretomanid and delamanid. By quantifying intracellular F420 and its precursor Fo in overexpressing and loss-of-function mutants, we provide further evidence that Rv2983 is necessary for F420 biosynthesis. Finally, Rv2983 mutants and other F420H2-deficient mutants displayed hypersusceptibility to some antibiotics and to concentrations of malachite green found in solid media used to isolate and propagate mycobacteria from clinical samples.

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The Serratia marcescens Siderophore Serratiochelin Is Necessary for Full Virulence during Bloodstream Infection

Infection and Immunity ◽

10.1128/iai.00117-20 ◽

2020 ◽

Vol 88 (8) ◽

Cited By ~ 1

Author(s):

Danelle R. Weakland ◽

Sara N. Smith ◽

Bailey Bell ◽

Ashootosh Tripathi ◽

Harry L. T. Mobley

Keyword(s):

Serratia Marcescens ◽

Bloodstream Infection ◽

Iron Acquisition ◽

Gene Clusters ◽

Clinical Isolates ◽

Wild Type ◽

Serratia Plymuthica ◽

Content Type ◽

Cas Assay ◽

Essential Nutrient

ABSTRACT Serratia marcescens is a bacterium frequently found in the environment, but over the last several decades it has evolved into a concerning clinical pathogen, causing fatal bacteremia. To establish such infections, pathogens require specific nutrients; one very limited but essential nutrient is iron. We sought to characterize the iron acquisition systems in S. marcescens isolate UMH9, which was recovered from a clinical bloodstream infection. Using RNA sequencing (RNA-seq), we identified two predicted siderophore gene clusters (cbs and sch) that were regulated by iron. Mutants were constructed to delete each iron acquisition locus individually and in conjunction, generating both single and double mutants for the putative siderophore systems. Mutants lacking the sch gene cluster lost their iron-chelating ability as quantified by the chrome azurol S (CAS) assay, whereas the cbs mutant retained wild-type activity. Mass spectrometry-based analysis identified the chelating siderophore to be serratiochelin, a siderophore previously identified in Serratia plymuthica. Serratiochelin-producing mutants also displayed a decreased growth rate under iron-limited conditions created by dipyridyl added to LB medium. Additionally, mutants lacking serratiochelin were significantly outcompeted during cochallenge with wild-type UMH9 in the kidneys and spleen after inoculation via the tail vein in a bacteremia mouse model. This result was further confirmed by an independent challenge, suggesting that serratiochelin is required for full S. marcescens pathogenesis in the bloodstream. Nine other clinical isolates have at least 90% protein identity to the UMH9 serratiochelin system; therefore, our results are broadly applicable to emerging clinical isolates of S. marcescens causing bacteremia.

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