Acinetobacter baumannii
                    Coordinates Urea Metabolism with Metal Import To Resist Host-Mediated Metal Limitation

ABSTRACT During infection, bacterial pathogens must adapt to a nutrient metal-limited environment that is imposed by the host. The innate immune protein calprotectin inhibits bacterial growth in vitro by chelating the divalent metal ions zinc (Zn 2+ , Zn) and manganese (Mn 2+ , Mn), but pathogenic bacteria are able to cause disease in the presence of this antimicrobial protein in vivo. One such pathogen is Acinetobacter baumannii , a Gram-negative bacterium that causes pneumonia and bloodstream infections that can be complicated by resistance to multiple antibiotics. A. baumannii inhibition by calprotectin is dependent on calprotectin Mn binding, but the mechanisms employed by A. baumannii to overcome Mn limitation have not been identified. This work demonstrates that A. baumannii coordinates transcription of an NRAMP family Mn transporter and a urea carboxylase to resist the antimicrobial activities of calprotectin. This NRAMP family transporter facilitates Mn accumulation and growth of A. baumannii in the presence of calprotectin. A. baumannii is found to utilize urea as a sole nitrogen source, and urea utilization requires the urea carboxylase encoded in an operon with the NRAMP family transporter. Moreover, urea carboxylase activity is essential for calprotectin resistance in A. baumannii . Finally, evidence is provided that this system combats calprotectin in vivo , as deletion of the transporter impairs A. baumannii fitness in a mouse model of pneumonia, and this fitness defect is modulated by the presence of calprotectin. These findings reveal that A. baumannii has evolved mechanisms to subvert host-mediated metal sequestration and they uncover a connection between metal starvation and metabolic stress. IMPORTANCE Acinetobacter baumannii is a bacterium that causes bloodstream, wound, urinary tract, and pneumonia infections, with a high disease burden in intensive care units. Treatment of A. baumannii infection is complicated by resistance to most antibiotics in use today, and resistance to last-resort therapies has become commonplace. New treatments for A. baumannii infection are desperately needed, but our current understanding of the bacterial factors required to cause infection is limited. We previously found that the abundant innate immune protein calprotectin inhibits the growth of A. baumannii by withholding essential metals . Despite this, A. baumannii is still able to infect wild-type mice, which produce calprotectin during infection. Here, we identify factors employed by A. baumannii during infection to overcome calprotectin-mediated metal sequestration. Moreover, we expose a connection between metal starvation and metabolism that may be a “chink in the armor” of A. baumannii and lead to new treatment options.

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In Vitro Activities of Various Antimicrobials Alone and in Combination with Tigecycline against Carbapenem-Intermediate or -Resistant Acinetobacter baumannii

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01099-06 ◽

2007 ◽

Vol 51 (5) ◽

pp. 1621-1626 ◽

Cited By ~ 67

Author(s):

Marc H. Scheetz ◽

Chao Qi ◽

John R. Warren ◽

Michael J. Postelnick ◽

Teresa Zembower ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Antimicrobial Susceptibility ◽

Bloodstream Infections ◽

Polymyxin B ◽

In Vitro Susceptibility ◽

Carbapenem Resistant ◽

Susceptibility Profiles ◽

Time Kill

ABSTRACT The activities of tigecycline alone and in combination with other antimicrobials are not well defined for carbapenem-intermediate or -resistant Acinetobacter baumannii (CIRA). Pharmacodynamic activity is even less well defined when clinically achievable serum concentrations are considered. Antimicrobial susceptibility testing of clinical CIRA isolates from 2001 to 2005 was performed by broth or agar dilution, as appropriate. Tigecycline concentrations were serially increased in time-kill studies with a representative of the most prevalent carbapenem-resistant clone (strain AA557; imipenem MIC, 64 mg/liter). The in vitro susceptibility of the strain was tested by time-kill studies in duplicate against the average free serum steady-state concentrations of tigecycline alone and in combination with various antimicrobials. Ninety-three CIRA isolates were tested and were found to have the following antimicrobial susceptibility profiles: tigecycline, MIC50 of 1 mg/liter and MIC90 of 2 mg/liter; minocycline, MIC50 of 0.5 mg/liter and MIC90 of 8 mg/liter; doxycycline, MIC50 of 2 mg/liter and MIC90 of ≥32 mg/liter; ampicillin-sulbactam, MIC50 of 48 mg/liter and MIC90 of 96 mg/liter; ciprofloxacin, MIC50 of ≥16 mg/liter and MIC90 of ≥16 mg/liter; rifampin, MIC50 of 4 mg/liter and MIC90 of 8 mg/liter; polymyxin B, MIC50 of 1 mg/liter and MIC90 of 1 mg/liter; amikacin, MIC50 of 32 mg/liter and MIC90 of ≥32 mg/liter; meropenem, MIC50 of 16 mg/liter and MIC90 of ≥128 mg/liter; and imipenem, MIC50 of 4 mg/liter and MIC90 of 64 mg/liter. Among the tetracyclines, the isolates were more susceptible to tigecycline than minocycline and doxycycline, according to FDA breakpoints (95%, 88%, and 71% of the isolates were susceptible to tigecycline, minocycline, and doxycycline, respectively). Concentration escalation studies with tigecycline revealed a maximal killing effect near the MIC, with no additional extent or rate of killing at concentrations 2× to 4× the MIC for tigecycline. Time-kill studies demonstrated indifference for tigecycline in combination with the antimicrobials tested. Polymyxin B, minocycline, and tigecycline are the most active antimicrobials in vitro against CIRA. Concentration escalation studies demonstrate that tigecycline may need to approach concentrations higher than those currently achieved in the bloodstream to adequately treat CIRA bloodstream infections. Future studies should evaluate these findings in vivo.

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In vitro and in vivo efficacy of the combination of colistin and endolysins against clinical strains of Multi-Drug Resistant (MDR) pathogens

10.1101/662460 ◽

2019 ◽

Author(s):

L. Blasco ◽

A. Ambroa ◽

R. Trastoy ◽

E. Perez-Nadales ◽

F. Fernández-Cuenca ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antimicrobial Activity ◽

Klebsiella Pneumoniae ◽

Acinetobacter Baumannii ◽

Bactericidal Activity ◽

Pathogenic Bacteria ◽

Galleria Mellonella ◽

Clinical Strain

ABSTRACTThe multidrug resistance (MDR) among pathogenic bacteria is jeopardizing the worth of antimicrobials, which had previously changed medical sciences. In this study, we used bioinformatic tools to identify the endolysins ElyA1 and ElyA2 (GH108-PG3 family) present in the genome of bacteriophages Ab1051Φ and Ab1052Φ, respectively. The muralytic activity of these endolysins over MDR clinical isolates (Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae) was tested using the turbidity reduction assay. The minimal inhibitory concentrations (MICs) of endolysin, colistin and their combination were determined using the microdilution checkerboard method. The antimicrobial activity of the combinations was confirmed by time kill curves and in vivo assays in larvae of Galleria mellonella. Our results showed that ElyA1 displayed activity against all 25 strains of A. baumannii and P. aeruginosa tested and against 13 out of 17 strains of K. pneumoniae. No activity was detected when assays were done with endolysin ElyA2. The combined antimicrobial activity of colistin and endolysin ElyA1 yielded a reduction in the colistin MIC for all strains studied, except K. pneumoniae. These results were confirmed in vivo in G. mellonella survival assays. In conclusion, the combination of colistin with new endolysins such as ElyA1 could increase the bactericidal activity and reduce the MIC of the antibiotic, thus also reducing the associated toxicity.IMPORTANCEThe development of multiresistance by pathogen bacteria increases the necessity of the development of new antimicrobial strategies. In this work, we combined the effect of the colistin with a new endolysin, ElyA1, from a bacteriophage present in the clinical strain of Acinetobacter baumannii Ab105. ElyA1 is a lysozyme-like family (GH108-GP3), whose antimicrobial activity was described for first time in this work. Also, another endolysin, ElyA2, with the same origin and family, was characterized but in this case no activity was detected. ElyA1 presented lytic activity over a broad spectrum of strains from A. baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. When colistin was combined with ElyA1 an increase of the antimicrobial activity was observed with a reduced concentration of colistin, and this observation was also confirmed in vivo in Galleria mellonella larvae. The combination of colistin with new endolysins as ElyA1 could increase the bactericidal activity and lowering the MIC of the antibiotic, thus also reducing the associated toxicity.

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Iron/Heme Metabolism-Targeted Gallium(III) Nanoparticles Are Active against Extracellular and Intracellular Pseudomonas aeruginosa and Acinetobacter baumannii

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02643-18 ◽

2019 ◽

Vol 63 (4) ◽

Cited By ~ 9

Author(s):

Seoung-ryoung Choi ◽

Bradley E. Britigan ◽

Prabagaran Narayanasamy

Keyword(s):

Pseudomonas Aeruginosa ◽

Acinetobacter Baumannii ◽

Iron Acquisition ◽

Antimicrobial Activities ◽

Antibiofilm Activity ◽

Content Type ◽

Gallium Concentration ◽

Iron Heme

ABSTRACT Iron/heme acquisition systems are critical for microorganisms to acquire iron from the human host, where iron sources are limited due to the nutritional immune system and insolubility of the ferric form of iron. Prior work has shown that a variety of gallium compounds can interfere with bacterial iron acquisition. This study explored the intra- and extracellular antimicrobial activities of gallium protoporphyrin (GaPP), gallium mesoporphyrin (GaMP), and nanoparticles encapsulating GaPP or GaMP against the Gram-negative pathogens Pseudomonas aeruginosa and Acinetobacter baumannii, including clinical isolates. All P. aeruginosa and A. baumannii isolates were susceptible to GaPP and GaMP, with MICs ranging from 0.5 to ∼32 μg/ml in iron-depleted medium. Significant intra- and extracellular growth inhibition was observed against P. aeruginosa cultured in macrophages at a gallium concentration of 3.3 μg/ml (5 μM) of all Ga(III) compounds, including nanoparticles. Nanoparticle formulations showed prolonged activity against both P. aeruginosa and A. baumannii in previously infected macrophages. When the macrophages were loaded with the nanoparticles 3 days prior to infection, there was a 5-fold decrease in growth of P. aeruginosa in the presence of single emulsion F127 copolymer nanoparticles encapsulating GaMP (eFGaMP). In addition, all Ga(III) porphyrins and nanoparticles showed significant intracellular and antibiofilm activity against both pathogens, with the nanoparticles exhibiting intracellular activity for 3 days. Ga nanoparticles also increased the survival rate of Caenorhabditis elegans nematodes infected by P. aeruginosa and A. baumannii. Our results demonstrate that Ga nanoparticles have prolonged in vitro and in vivo activities against both P. aeruginosa and A. baumannii, including disruption of their biofilms.

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An Organoselenium Compound Inhibits Staphylococcus aureus Biofilms on Hemodialysis CathetersIn Vivo

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05680-11 ◽

2011 ◽

Vol 56 (2) ◽

pp. 972-978 ◽

Cited By ~ 52

Author(s):

Phat L. Tran ◽

Nathan Lowry ◽

Thomas Campbell ◽

Ted W. Reid ◽

Daniel R. Webster ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Pathogenic Bacteria ◽

Antimicrobial Agents ◽

Bloodstream Infections ◽

Organoselenium Compound ◽

Central Venous ◽

Antibiotic Resistant ◽

Content Type

ABSTRACTColonization of central venous catheters (CVCs) by pathogenic bacteria leads to catheter-related bloodstream infections (CRBSIs). These colonizing bacteria form highly antibiotic-resistant biofilms.Staphylococcus aureusis one of the most frequently isolated pathogens in CRBSIs. Impregnating CVC surfaces with antimicrobial agents has various degrees of effectiveness in reducing the incidence of CRBSIs. We recently showed that organoselenium covalently attached to disks as an antibiofilm agent inhibited the development ofS. aureusbiofilms. In this study, we investigated the ability of an organoselenium coating on hemodialysis catheters (HDCs) to inhibitS. aureusbiofilmsin vitroandin vivo.S. aureusfailed to develop biofilms on HDCs coated with selenocyanatodiacetic acid (SCAA) in either static or flowthrough continuous-culture systems. The SCAA coating also inhibited the development ofS. aureusbiofilms on HDCsin vivofor 3 days. The SCAA coating was stable and nontoxic to cell culture or animals. This new method for coating the internal and external surfaces of HDCs with SCAA has the potential to prevent catheter-related infections due toS. aureus.

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ANTIMICROBIAL ACTIVITY OF CALLYSPONGIA DIFFUSA (MARINE SPONGE) ASSOCIATED ENDOPHYTIC BACTERIA L STRAINS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i7.18480 ◽

2017 ◽

Vol 9 (7) ◽

pp. 90

Author(s):

Vijayanand B. Warad ◽

Prasanna Habbu ◽

Rajesh Shastri

Keyword(s):

Antimicrobial Activity ◽

Marine Sponge ◽

Pathogenic Bacteria ◽

Antimicrobial Activities ◽

Bioactive Metabolites ◽

Haemolytic Activity ◽

Chloroform Fraction ◽

Callyspongia Diffusa

Objective: To screen the antimicrobial activity Of Callyspongia Diffusa (Marine Sponge) Associated Endophytic Bacterial Strains.Methods: We have isolated endophytic bacterias CDB-1 and CDB-2 from marine sponge Callyspongia diffusa and identified as Pseudomonas taiwanensis strain and Lysinibacillussphaericus strain respectively by the phylogenetic analysis. Fractions of CDB-1 and CDB-2 were screened for in vitro and in vivo antimicrobial activities against pathogenic bacteria and mycobacterium tuberculosis H37 RV strain by Minimum Inhibitory Concentration (MIC) method.Results: The lowest MIC against Kleibesella pnumoniae, Escherichia coli and Enterococcus feacalis was found to be 0.2 µg/ml and 0.4 µg/ml respectively for CDB-2. A significant antifungal activity was observed against Candida albicans (0.2-0.8 µg/ml) and Aspergillus niger (0.2-0.4 µg/ml). Further, Chloroform fraction of CDB-1 and ethyl acetate fraction of CDB-2 have shown significant anti-tubercular activity against the tested organism with MIC of 6.25µg/ml. This was supported by in vivo antimicrobial activity against K. Pneumonia infection in mice and least haemolytic activity against erythrocytes was observed. Compared to chloramphenicol.Conclusion: In this study, we have reported the marine natural species offer a rich source of bioactive metabolites that can exploit to develop novel, useful and potential therapeutic agents.

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Prospective Application of Aptamer-based Assays and Therapeutics in Bloodstream Infections

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666200212105813 ◽

2020 ◽

Vol 20 (10) ◽

pp. 831-840

Author(s):

Weibin Li

Keyword(s):

Pathogenic Bacteria ◽

Genetic Diagnosis ◽

Bloodstream Infections ◽

High Specificity ◽

Peptide Sequence ◽

High Morbidity ◽

Specificity And Sensitivity ◽

Prospective Application ◽

Small Molecule Therapeutics

Sepsis is still a severe health problem worldwide with high morbidity and mortality. Blood bacterial culture remains the gold standard for the detection of pathogenic bacteria in bloodstream infections, but it is time-consuming, and both the sophisticated equipment and well-trained personnel are required. Immunoassays and genetic diagnosis are expensive and limited to specificity and sensitivity. Aptamers are single-stranded deoxyribonucleic acid (ssDNA) and ribonucleic acid (RNA) oligonucleotide or peptide sequence generated in vitro based on the binding affinity of aptamer-target by a process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX). By taking several advantages over monoclonal antibodies and other conventional small-molecule therapeutics, such as high specificity and affinity, negligible batch-to-batch variation, flexible modification and production, thermal stability, low immunogenicity and lack of toxicity, aptamers are presently becoming promising novel diagnostic and therapeutic agents. This review describes the prospective application of aptamerbased laboratory diagnostic assays and therapeutics for pathogenic bacteria and toxins in bloodstream infections.

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Synthesis of Novel 3(N,N-dialkylamino)alkyl/phenyl Substituted Thieno [2,3-d]pyrimidinones as H1-Anti-Histaminic and Antimicrobial Agents

Current Bioactive Compounds ◽

10.2174/1573407214666180226130957 ◽

2019 ◽

Vol 15 (1) ◽

pp. 63-70

Author(s):

Shiv Dev Singh ◽

Arvind Kumar ◽

Firoz Babar ◽

Neetu Sachan ◽

Arun Kumar Sharma

Keyword(s):

Antimicrobial Activity ◽

Potassium Hydroxide ◽

Antimicrobial Agents ◽

Pyrimidine Ring ◽

Antimicrobial Activities ◽

Screening Methods ◽

Chlorpheniramine Maleate ◽

In Vivo Screening

Background: Thienopyrimidines are the bioisoster of quinazoline and unlike quinazoline exist in three isomeric forms corresponding to the three possible types annulation of thiophene to the pyrimidine ring viz thieno[2,3-d] pyrimidine, thieno[3,2-d] pyrimidine and thieno[3,4-d]pyrimidine. Heterocyclic containing the thienopyrimidinone moiety exhibits various pronounced activities such as anti-hypertensive, analgesic and anti-inflammatory, antiviral, platelet aggregation inhibitory, antiprotozoal bronchodilatory, phosphodiesterase inhibitory, antihistaminic, antipsychotic and antimicrobial activity. Objective: Synthesis of novel 3(N,N-dialkylamino)alkyl/phenyl substituted thieno[2,3-d]pyrimidinones as H1-anti-histaminic and antimicrobial agents. Methods: A series of 3-[(N,N-dialkylamino)alkyl/phenyl]-2-(1H)thioxo-5,6,7,8-tetrahydrobenzo(b) thieno(2,3-d)pyrimidine-4(3H)-ones[4a-d], their oxo analogous [5a-d] and 3-[(N,N-dialkylamino)alkyl]- 2-chlorophenyl-5,6,7,8-tetrahydrobenzo(b)thieno(2,3-d)pyrimidine- 4 (3H)-ones[6a-d]derivative were synthesized from 2-amino-4,5,6,7-tetrahydrobenzo(b)thiophene-3-carboxylic acid by nucleophilic substitution of different N,N-dialkyl alkylene/phenylene diamines on activated 3-acylchloride moiety followed by cyclocondensation with carbon disulfide and ethanolic potassium hydroxide to get [4a-d] and in second reaction by condensation with 4-chlorobenzoyl chloride to get [6a-d] by single pot novel innovative route. The oxo analogous [5a-d] were prepared by treating derivatives [4a-d] with potassium permagnate in ethanolic KOH. The synthesized compound were evaluated for H1-antihistaminic and antimicrobial activities. Results: All synthesized compounds exhibited significant H1-antihistaminic activity by in vitro and in vivo screening methods and data were verified analytically and statistically. The compound 4a, 4b, 5a and 5b showed significant H1-antihistaminiic activity than the reference standard chlorpheniramine maleate. The compound 6d, 6c, 5c and 4c exhibited significant antimicrobial activity.

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Targeting Toll-Like Receptor 2: Polarization of Porcine Macrophages by a Mycoplasma-Derived Pam2cys Lipopeptide

Vaccines ◽

10.3390/vaccines9070692 ◽

2021 ◽

Vol 9 (7) ◽

pp. 692

Author(s):

Giulia Franzoni ◽

Antonio Anfossi ◽

Chiara Grazia De Ciucis ◽

Samanta Mecocci ◽

Tania Carta ◽

...

Keyword(s):

Mhc Class Ii ◽

Macrophage Polarization ◽

Surface Protein ◽

Antimicrobial Activities ◽

Toll Like Receptor ◽

Activation Markers ◽

Class I Mhc ◽

Toll Like Receptor 2

Toll-like receptor 2 (TLR2) ligands are attracting increasing attention as prophylactic and immunotherapeutic agents against pathogens and tumors. We previously observed that a synthetic diacylated lipopeptide based on a surface protein of Mycoplasma agalactiae (Mag-Pam2Cys) strongly activated innate immune cells, including porcine monocyte-derived macrophages (moMΦ). In this study, we utilized confocal microscopy, flow cytometry, multiplex cytokine ELISA, and RT-qPCR to conduct a comprehensive analysis of the effects of scalar doses of Mag-Pam2Cys on porcine moMΦ. We observed enhanced expression of activation markers (MHC class I, MHC class II DR, CD25), increased phagocytotic activity, and release of IL-12 and proinflammatory cytokines. Mag-Pam2Cys also upregulated the gene expression of several IFN-α subtypes, p65, NOS2, and molecules with antimicrobial activities (CD14, beta defensin 1). Overall, our data showed that Mag-Pam2Cys polarized porcine macrophages towards a proinflammatory antimicrobial phenotype. However, Mag-Pam2Cys downregulated the expression of IFN-α3, six TLRs (TLR3, -4, -5, -7, -8, -9), and did not interfere with macrophage polarization induced by the immunosuppressive IL-10, suggesting that the inflammatory activity evoked by Mag-Pam2Cys could be regulated to avoid potentially harmful consequences. We hope that our in vitro results will lay the foundation for the further evaluation of this diacylated lipopeptide as an immunopotentiator in vivo.

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Cerebrospinal fluid (CSF) augments metabolism and virulence expression factors in Acinetobacter baumannii

Scientific Reports ◽

10.1038/s41598-021-81714-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jasmine Martinez ◽

Chelsea Razo-Gutierrez ◽

Casin Le ◽

Robert Courville ◽

Camila Pimentel ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Acinetobacter Baumannii ◽

Virulence Factors ◽

Atp Synthesis ◽

Bloodstream Infections ◽

Model Systems ◽

Phenotypic Traits ◽

Virulence Determinants ◽

Expression Of Genes

AbstractIn a recent report by the Centers for Disease Control and Prevention (CDC), multidrug resistant (MDR) Acinetobacter baumannii is a pathogen described as an “urgent threat.” Infection with this bacterium manifests as different diseases such as community and nosocomial pneumonia, bloodstream infections, endocarditis, infections of the urinary tract, wound infections, burn infections, skin and soft tissue infections, and meningitis. In particular, nosocomial meningitis, an unwelcome complication of neurosurgery caused by extensively-drug resistant (XDR) A. baumannii, is extremely challenging to manage. Therefore, understanding how A. baumannii adapts to different host environments, such as cerebrospinal fluid (CSF) that may trigger changes in expression of virulence factors that are associated with the successful establishment and progress of this infection is necessary. The present in-vitro work describes, the genetic changes that occur during A. baumannii infiltration into CSF and displays A. baumannii’s expansive versatility to persist in a nutrient limited environment while enhancing several virulence factors to survive and persist. While a hypervirulent A. baumannii strain did not show changes in its transcriptome when incubated in the presence of CSF, a low-virulence isolate showed significant differences in gene expression and phenotypic traits. Exposure to 4% CSF caused increased expression of virulence factors such as fimbriae, pilins, and iron chelators, and other virulence determinants that was confirmed in various model systems. Furthermore, although CSF's presence did not enhance bacterial growth, an increase of expression of genes encoding transcription, translation, and the ATP synthesis machinery was observed. This work also explores A. baumannii’s response to an essential component, human serum albumin (HSA), within CSF to trigger the differential expression of genes associated with its pathoadaptibility in this environment.

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Staphylococcus aureus Serves as an Iron Source for Pseudomonas aeruginosa during In Vivo Coculture

Journal of Bacteriology ◽

10.1128/jb.187.2.554-566.2005 ◽

2005 ◽

Vol 187 (2) ◽

pp. 554-566 ◽

Cited By ~ 174

Author(s):

Lauren M. Mashburn ◽

Amy M. Jett ◽

Darrin R. Akins ◽

Marvin Whiteley

Keyword(s):

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Pathogenic Bacteria ◽

Iron Acquisition ◽

Low Oxygen ◽

Dialysis Membrane ◽

Opportunistic Human Pathogen ◽

The Impact

ABSTRACT Pseudomonas aeruginosa is a gram-negative opportunistic human pathogen often infecting the lungs of individuals with the heritable disease cystic fibrosis and the peritoneum of individuals undergoing continuous ambulatory peritoneal dialysis. Often these infections are not caused by colonization with P. aeruginosa alone but instead by a consortium of pathogenic bacteria. Little is known about growth and persistence of P. aeruginosa in vivo, and less is known about the impact of coinfecting bacteria on P. aeruginosa pathogenesis and physiology. In this study, a rat dialysis membrane peritoneal model was used to evaluate the in vivo transcriptome of P. aeruginosa in monoculture and in coculture with Staphylococcus aureus. Monoculture results indicate that approximately 5% of all P. aeruginosa genes are differentially regulated during growth in vivo compared to in vitro controls. Included in this analysis are genes important for iron acquisition and growth in low-oxygen environments. The presence of S. aureus caused decreased transcription of P. aeruginosa iron-regulated genes during in vivo coculture, indicating that the presence of S. aureus increases usable iron for P. aeruginosa in this environment. We propose a model where P. aeruginosa lyses S. aureus and uses released iron for growth in low-iron environments.

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