Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Gut Pathogens
Published in: Gut Pathogens 1/2018

Open Access 01-12-2018 | Research

Identification of a new alanine racemase in Salmonella Enteritidis and its contribution to pathogenesis

Authors: Shilpa Ray, Susmita Das, Pritam Kumar Panda, Mrutyunjay Suar

Published in: Gut Pathogens | Issue 1/2018

Login to get access

Abstract

Background

Non-typhoidal Salmonella (NTS) infections caused primarily by S. Enteritidis and S. Typhimurium particularly in immunocompromised hosts have accounted for a large percentage of fatalities in developed nations. Antibiotics have revolutionized the cure of enteric infections but have also led to the rapid emergence of pathogen resistance. New powerful therapeutics involving metabolic enzymes are expected to be potential targets for combating microbial infections and ensuring effective health management. Therefore, the need for new antimicrobials to fight such health emergencies is paramount. Enteric bacteria successfully evade the gut and colonize their hosts through specialized virulence strategies. An important player, alanine racemase is a key enzyme facilitating bacterial survival.

Results

This study aims at understanding the contribution of alanine racemase genes alr, dadX and SEN3897 to Salmonella survival in vitro and in vivo. We have shown SEN3897 to function as a unique alanine racemase in S. Enteritidis which displayed essential alanine racemase activity. Interestingly, the sole presence of this gene in alr dadX double mutant showed a strict dependence on d-alanine supplementation both in vitro and in vivo. However, Alr complementation in d-alanine auxotrophic strain restored the alanine racemase deficiency. The Km and Vmax of SEN3897 was 89.15 ± 10.2 mM, 400 ± 25.6 µmol/(min mg) for l-alanine and 35 ± 6 mM, 132.5 ± 11.3 µmol/(min mg) for d-alanine, respectively. In vitro assays for invasion and survival as well as in vivo virulence assays involving SEN3897 mutant showed attenuated phenotypes. Further, this study also showed attenuation of d-alanine auxotrophic strain in vivo for the development of potential targets against Salmonella that can be investigated further.

Conclusion

This study identified a third alanine racemase gene unique in S. Enteritidis which had a potential effect on survival and pathogenesis in vitro and in vivo. Our results also confirmed that SEN3897 by itself wasn’t able to rescue d-alanine auxotrophy in S. Enteritidis which further contributed to its virulence properties.
Appendix
Available only for authorised users
Literature
1.
Chimalizeni Y, Kawaza K, Molyneux E. The epidemiology and management of non typhoidal salmonella infections. In: Finn A, Curtis N, Pollard A, editors. Hot topics in infection and immunity in children VI. Advances in experimental medicine and biology. Vol 659. New York, NY: Springer; 2010. pp. 33–46. https://​doi.​org/​10.​1007/​978-1-4419-0981-7_​3.CrossRef
2.
Eswarappa SM, Janice J, Nagarajan AG, Balasundaram SV, Karnam G, Dixit NM, Chakravortty D. Differentially evolved genes of Salmonella pathogenicity islands: insights into the mechanism of host specificity in Salmonella. PLoS ONE. 2008;3(12):e3829.CrossRefPubMedPubMedCentral
3.
Majowicz SE, Musto J, Scallan E, Angulo FJ, Kirk M, O’brien SJ, Jones TF, Fazil A, Hoekstra RM. The global burden of nontyphoidal Salmonella gastroenteritis. Clin Infect Dis. 2010;50(6):882–9.CrossRefPubMed
4.
5.
Ibarra JA, Steele-Mortimer O. Salmonella—the ultimate insider. Salmonella virulence factors that modulate intracellular survival. Cell Microbiol. 2009;11(11):1579–86.CrossRefPubMedPubMedCentral
6.
7.
Lostroh CP, Lee CA. The Salmonella pathogenicity island-1 type III secretion system. Microbes Infect. 2001;3(14):1281–91.CrossRefPubMed
8.
Waterman SR, Holden DW. Functions and effectors of the Salmonella pathogenicity island 2 type III secretion system. Cell Microbiol. 2003;5(8):501–11.CrossRefPubMed
9.
10.
Galán JE. Salmonella interactions with host cells: type III secretion at work. Annu Rev Cell Dev Biol. 2001;17(1):53–86.CrossRefPubMed
11.
12.
13.
Hennessy TW, Hedberg CW, Slutsker L, White KE, Besser-Wiek JM, Moen ME, Feldman J, Coleman WW, Edmonson LM, MacDonald KL. A national outbreak of Salmonella enteritidis infections from ice cream. N Engl J Med. 1996;334(20):1281–6.CrossRefPubMed
14.
Chan K, Kim CC, Falkow S. Microarray-based detection of Salmonella enterica serovar Typhimurium transposon mutants that cannot survive in macrophages and mice. Infect Immun. 2005;73(9):5438–49.CrossRefPubMedPubMedCentral
15.
Chaudhuri RR, Peters SE, Pleasance SJ, Northen H, Willers C, Paterson GK, Cone DB, Allen AG, Owen PJ, Shalom G. Comprehensive identification of Salmonella enterica serovar typhimurium genes required for infection of BALB/c mice. PLoS Pathog. 2009;5(7):e1000529.CrossRefPubMedPubMedCentral
16.
Lawley TD, Chan K, Thompson LJ, Kim CC, Govoni GR, Monack DM. Genome-wide screen for Salmonella genes required for long-term systemic infection of the mouse. PLoS Pathog. 2006;2(2):e11.CrossRefPubMedPubMedCentral
17.
Santiviago CA, Reynolds MM, Porwollik S, Choi S-H, Long F, Andrews-Polymenis HL, McClelland M. Analysis of pools of targeted Salmonella deletion mutants identifies novel genes affecting fitness during competitive infection in mice. PLoS Pathog. 2009;5(7):e1000477.CrossRefPubMedPubMedCentral
18.
Vishwakarma V, Periaswamy B, Pati NB, Slack E, Hardt W-D, Suar M. A novel phage element of Salmonella enterica serovar Enteritidis P125109 contributes to accelerated type III secretion system 2-dependent early inflammation kinetics in a mouse colitis model. Infect Immun. 2012;80(9):3236–46.CrossRefPubMedPubMedCentral
19.
Suar M, Periaswamy B, Songhet P, Misselwitz B, Müller A, Käppeli R, Kremer M, Heikenwalder M, Hardt W-D. Accelerated type III secretion system 2-dependent enteropathogenesis by a Salmonella enterica serovar enteritidis PT4/6 strain. Infect Immun. 2009;77(9):3569–77.CrossRefPubMedPubMedCentral
20.
Silva CA, Blondel CJ, Quezada CP, Porwollik S, Andrews-Polymenis HL, Toro CS, Zaldívar M, Contreras I, McClelland M, Santiviago CA. Infection of mice by Salmonella enterica serovar Enteritidis involves additional genes that are absent in the genome of serovar Typhimurium. Infect Immun. 2012;80(2):839–49.CrossRefPubMedPubMedCentral
21.
Di Salvo ML, Florio R, Paiardini A, Vivoli M, D’Aguanno S, Contestabile R. Alanine racemase from Tolypocladium inflatum: a key PLP-dependent enzyme in cyclosporin biosynthesis and a model of catalytic promiscuity. Arch Biochem Biophys. 2013;529(2):55–65.CrossRefPubMed
22.
Hols P, Defrenne C, Ferain T, Derzelle S, Delplace B, Delcour J. The alanine racemase gene is essential for growth of Lactobacillus plantarum. J Bacteriol. 1997;179(11):3804–7.CrossRefPubMedPubMedCentral
23.
Strych U, Huang H-C, Krause KL, Benedik MJ. Characterization of the alanine racemases from Pseudomonas aeruginosa PAO1. Curr Microbiol. 2000;41(4):290–4.CrossRefPubMed
24.
Strych U, Penland RL, Jimenez M, Krause KL, Benedik MJ. Characterization of the alanine racemases from two mycobacteria. FEMS Microbiol Lett. 2001;196(2):93–8.CrossRefPubMed
25.
Strych U, Davlieva M, Longtin JP, Murphy EL, Im H, Benedik MJ, Krause KL. Purification and preliminary crystallization of alanine racemase from Streptococcus pneumoniae. BMC Microbiol. 2007;7(1):40.CrossRefPubMedPubMedCentral
26.
Wasserman SA, Walsh CT, Botstein D. Two alanine racemase genes in Salmonella typhimurium that differ in structure and function. J Bacteriol. 1983;153(3):1439–50.PubMedPubMedCentral
27.
Anthony KG, Strych U, Yeung KR, Shoen CS, Perez O, Krause KL, Cynamon MH, Aristoff PA, Koski RA. New classes of alanine racemase inhibitors identified by high-throughput screening show antimicrobial activity against Mycobacterium tuberculosis. PLoS ONE. 2011;6(5):e20374.CrossRefPubMedPubMedCentral
28.
Datsenko KA, Wanner BL. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci. 2000;97(12):6640–5.CrossRefPubMed
29.
Seo E-Y, Ahn T-S, Zo Y-G. Agreement, precision, and accuracy of epifluorescence microscopy methods for enumeration of total bacterial numbers. Appl Environ Microbiol. 2010;76(6):1981–91.CrossRefPubMedPubMedCentral
30.
Freese H, Karsten U, Schumann R. Bacterial abundance, activity, and viability in the eutrophic river Warnow, Northeast Germany. Microbial Ecology. 2006;51(1):117–27.CrossRefPubMed
31.
32.
Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605–12.CrossRefPubMed
33.
34.
Shibata K, Shirasuna K, Motegi K, Kera Y, Abe H. Yamada R-h: purification and properties of alanine racemase from crayfish Procambarus clarkii. Comp Biochem Physiol B Biochem Mol Biol. 2000;126(4):599–608.CrossRefPubMed
35.
Pati NB, Vishwakarma V, Jaiswal S, Periaswamy B, Hardt W-D, Suar M. Deletion of invH gene in Salmonella enterica serovar Typhimurium limits the secretion of Sip effector proteins. Microbes Infect. 2013;15(1):66–73.CrossRefPubMed
36.
Jaiswal S, Pati NB, Dubey M, Padhi C, Sahoo PK, Ray S, Arunima A, Mohakud NK, Suar M. The O-antigen negative∆ wbaV mutant of Salmonella enterica serovar Enteritidis shows adaptive resistance to antimicrobial peptides and elicits colitis in streptomycin pretreated mouse model. Gut Pathog. 2015;7(1):1.CrossRef
37.
Hölzer SU, Schlumberger MC, Jäckel D, Hensel M. Effect of the O-antigen length of lipopolysaccharide on the functions of type III secretion systems in Salmonella enterica. Infect Immun. 2009;77(12):5458–70.CrossRefPubMedPubMedCentral
38.
Jaiswal S, Sahoo PK, Ryan D, Das JK, Chakraborty E, Mohakud NK, Suar M. Altered virulence potential of Salmonella Enteritidis cultured in different foods: a cumulative effect of differential gene expression and immunomodulation. Int J Food Microbiol. 2016;230:64–72.CrossRefPubMed
39.
Barthel M, Hapfelmeier S, Quintanilla-Martínez L, Kremer M, Rohde M, Hogardt M, Pfeffer K, Rüssmann H, Hardt W-D. Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host. Infect Immun. 2003;71(5):2839–58.CrossRefPubMedPubMedCentral
40.
Prism G. Version 6.0 e. GraphPad Software; 2014.
41.
Palumbo E, Favier CF, Deghorain M, Cocconcelli PS, Grangette C, Mercenier A, Vaughan EE, Hols P. Knockout of the alanine racemase gene in Lactobacillus plantarum results in septation defects and cell wall perforation. FEMS Microbiol Lett. 2004;233(1):131–8.CrossRefPubMed
42.
Chacon O, Bermudez LE, Zinniel DK, Chahal HK, Fenton RJ, Feng Z, Hanford K, Adams LG, Barletta RG. Impairment of d-alanine biosynthesis in Mycobacterium smegmatis determines decreased intracellular survival in human macrophages. Microbiology. 2009;155(5):1440–50.CrossRefPubMed
43.
Awasthy D, Bharath S, Subbulakshmi V, Sharma U. Alanine racemase mutants of Mycobacterium tuberculosis require d-alanine for growth and are defective for survival in macrophages and mice. Microbiology. 2012;158(2):319–27.CrossRefPubMed
44.
Im H, Sharpe ML, Strych U, Davlieva M, Krause KL. The crystal structure of alanine racemase from Streptococcus pneumoniae, a target for structure-based drug design. BMC Microbiol. 2011;11(1):116.CrossRefPubMedPubMedCentral
45.
Wasserman SA, Daub E, Grisafi P, Botstein D, Walsh CT. Catabolic alanine racemase from Salmonella typhimurium: DNA sequence, enzyme purification, and characterization. Biochemistry. 1984;23(22):5182–7.CrossRefPubMed
46.
Esaki N, Walsh CT. Biosynthetic alanine racemase of Salmonella typhimurium: purification and characterization of the enzyme encoded by the alr gene. Biochemistry. 1986;25(11):3261–7.CrossRefPubMed
47.
48.
Thompson RJ, Bouwer HA, Portnoy DA, Frankel FR. Pathogenicity and immunogenicity of a Listeria monocytogenes strain that requires d-alanine for growth. Infect Immun. 1998;66(8):3552–61.PubMedPubMedCentral
49.
Milligan DL, Tran SL, Strych U, Cook GM, Krause KL. The alanine racemase of Mycobacterium smegmatis is essential for growth in the absence of d-alanine. J Bacteriol. 2007;189(22):8381–6.CrossRefPubMedPubMedCentral
50.
Moore BC, Leigh JA. Markerless mutagenesis in Methanococcus maripaludis demonstrates roles for alanine dehydrogenase, alanine racemase, and alanine permease. J Bacteriol. 2005;187(3):972–9.CrossRefPubMedPubMedCentral
51.
Zajdowicz SL, Jones-Carson J, Vazquez-Torres A, Jobling MG, Gill RE, Holmes RK. Alanine racemase mutants of Burkholderia pseudomallei and Burkholderia mallei and use of alanine racemase as a non-antibiotic-based selectable marker. PLoS ONE. 2011;6(6):e21523.CrossRefPubMedPubMedCentral
52.
Steen A, Palumbo E, Deghorain M, Cocconcelli PS, Delcour J, Kuipers OP, Kok J, Buist G, Hols P. Autolysis of Lactococcus lactis is increased upon d-alanine depletion of peptidoglycan and lipoteichoic acids. J Bacteriol. 2005;187(1):114–24.CrossRefPubMedPubMedCentral
53.
Shaw JP, Petsko GA, Ringe D. Determination of the structure of alanine racemase from Bacillus stearothermophilus at 1.9-Å resolution. Biochemistry. 1997;36(6):1329–42.CrossRefPubMed
54.
Stamper CGF, Morollo AA, Ringe D. Reaction of alanine racemase with 1-aminoethylphosphonic acid forms a stable external aldimine. Biochemistry. 1998;37(29):10438–45.CrossRefPubMed
55.
Morollo AA, Petsko GA, Ringe D. Structure of a Michaelis complex analogue: propionate binds in the substrate carboxylate site of alanine racemase. Biochemistry. 1999;38(11):3293–301.CrossRefPubMed
56.
Galakatos NG, Daub E, Botstein D, Walsh CT. Biosynthetic alr alanine racemase from Salmonella typhimurium: DNA and protein sequence determination. Biochemistry. 1986;25(11):3255–60.CrossRefPubMed
57.
LeMagueres P, Im H, Ebalunode J, Strych U, Benedik MJ, Briggs JM, Kohn H, Krause KL. The 1.9 Å crystal structure of alanine racemase from Mycobacterium tuberculosis contains a conserved entryway into the active site. Biochemistry. 2005;44(5):1471–81.CrossRefPubMed
58.
Patrick WM, Weisner J, Blackburn JM. Site-directed mutagenesis of Tyr354 in Geobacillus stearothermophilus alanine racemase identifies a role in controlling substrate specificity and a possible role in the evolution of antibiotic resistance. ChemBioChem. 2002;3(8):789–92.CrossRefPubMed
59.
60.
Crawford RM, Van De Verg L, Yuan L, Hadfield TL, Warren RL, Drazek ES, Houng H, Hammack C, Sasala K, Polsinelli T. Deletion of purE attenuates Brucella melitensis infection in mice. Infect Immun. 1996;64(6):2188–92.PubMedPubMedCentral
61.
Mintz CS, Chen J, Shuman HA. Isolation and characterization of auxotrophic mutants of Legionella pneumophila that fail to multiply in human monocytes. Infect Immun. 1988;56(6):1449–55.PubMedPubMedCentral
62.
Guleria I, Teitelbaum R, McAdam RA, Kalpana G, Jacobs WR, Bloom BR. Auxotrophic vaccines for tuberculosis. Nat Med. 1996;2(3):334–7.CrossRefPubMed
63.
Ellermeier JR, Slauch JM. Adaptation to the host environment: regulation of the SPI1 type III secretion system in Salmonella enterica serovar Typhimurium. Curr Opin Microbiol. 2007;10(1):24–9.CrossRefPubMed
64.
Kuhle V, Hensel M. Cellular microbiology of intracellular Salmonella enterica: functions of the type III secretion system encoded by Salmonella pathogenicity island 2. Cell Mol Life Sci CMLS. 2004;61(22):2812–26.CrossRefPubMed
65.
Olekhnovich IN, Kadner RJ. Role of nucleoid-associated proteins Hha and H-NS in expression of Salmonella enterica activators HilD, HilC, and RtsA required for cell invasion. J Bacteriol. 2007;189(19):6882–90.CrossRefPubMedPubMedCentral
66.
Fàbrega A, Vila J. Salmonella enterica serovar Typhimurium skills to succeed in the host: virulence and regulation. Clin Microbiol Rev. 2013;26(2):308–41.CrossRefPubMedPubMedCentral
67.
Ellermeier CD, Ellermeier JR, Slauch JM. HilD, HilC and RtsA constitute a feed forward loop that controls expression of the SPI1 type three secretion system regulator hilA in Salmonella enterica serovar Typhimurium. Mol Microbiol. 2005;57(3):691–705.CrossRefPubMed
68.
Bajaj V, Lucas RL, Hwang C, Lee CA. Co-ordinate regulation of Salmonella typhimurium invasion genes by environmental and regulatory factors is mediated by control of hilA expression. Mol Microbiol. 1996;22(4):703–14.CrossRefPubMed
69.
Darwin KH, Miller VL. InvF is required for expression of genes encoding proteins secreted by the SPI1 type III secretion apparatus in Salmonella typhimurium. J Bacteriol. 1999;181(16):4949–54.PubMed
70.
Akbar S, Schechter LM, Lostroh CP, Lee CA. AraC/XylS family members, HilD and HilC, directly activate virulence gene expression independently of HilA in Salmonella typhimurium. Mol Microbiol. 2003;47(3):715–28.CrossRefPubMed
71.
Brumell JH, Goosney DL, Finlay BB. SifA, a Type III secreted effector of Salmonella typhimurium, directs Salmonella-induced filament (Sif) formation along microtubules. Traffic. 2002;3(6):407–15.CrossRefPubMed
72.
Ruiz-Albert J, Yu XJ, Beuzón CR, Blakey AN, Galyov EE, Holden DW. Complementary activities of SseJ and SifA regulate dynamics of the Salmonella typhimurium vacuolar membrane. Mol Microbiol. 2002;44(3):645–61.CrossRefPubMed
73.
Miao EA, Miller SI. A conserved amino acid sequence directing intracellular type III secretion by Salmonella typhimurium. Proc Natl Acad Sci. 2000;97(13):7539–44.CrossRefPubMed
74.
Deiwick J, Salcedo SP, Boucrot E, Gilliland SM, Henry T, Petermann N, Waterman SR, Gorvel J-P, Holden DW, Méresse S. The translocated Salmonella effector proteins SseF and SseG interact and are required to establish an intracellular replication niche. Infect Immun. 2006;74(12):6965–72.CrossRefPubMedPubMedCentral
75.
Hapfelmeier S, Stecher B, Barthel M, Kremer M, Müller AJ, Heikenwalder M, Stallmach T, Hensel M, Pfeffer K, Akira S. The Salmonella pathogenicity island (SPI)-2 and SPI-1 type III secretion systems allow Salmonella serovar typhimurium to trigger colitis via MyD88-dependent and MyD88-independent mechanisms. J Immunol. 2005;174(3):1675–85.CrossRefPubMed
76.
Cersini A, Salvia AM, Bernardini ML. Intracellular multiplication and virulence of Shigella flexneri auxotrophic mutants. Infect Immun. 1998;66(2):549–57.PubMedPubMedCentral
77.
Bruning JB, Murillo AC, Chacon O, Barletta RG, Sacchettini JC. Structure of the Mycobacterium tuberculosis d-alanine: d-alanine ligase, a target of the antituberculosis drug d-cycloserine. Antimicrob Agents Chemother. 2011;55(1):291–301.CrossRefPubMed
78.
Moscoso M, García P, Cabral MP, Rumbo C, Bou G. A d-alanine auxotrophic live vaccine is effective against lethal infection caused by Staphylococcus aureus. Virulence. 2018;9(1):604–20.CrossRefPubMedPubMedCentral
79.
Jaiswal S, Pati NB, Dubey M, Padhi C, Sahoo PK, Ray S, Arunima A, Mohakud NK, Suar M. The O-antigen negative∆ wbaV mutant of Salmonella enterica serovar Enteritidis shows adaptive resistance to antimicrobial peptides and elicits colitis in streptomycin pretreated mouse model. Gut pathog. 2015;7(1):24.CrossRefPubMedPubMedCentral
80.
Pati NB, Vishwakarma V, kumar Selvaraj S, Dash S, Saha B, Singh N, Suar M. Salmonella Typhimurium TTSS-2 deficient mig-14 mutant shows attenuation in immunocompromised mice and offers protection against wild-type Salmonella Typhimurium infection. BMC Microbiol. 2013;13(1):1.CrossRef
81.
Das JK, Mishra D, Ray P, Tripathy P, Beuria TK, Singh N, Suar M. In vitro evaluation of anti-infective activity of a Lactobacillus plantarum strain against Salmonella enterica serovar Enteritidis. Gut pathog. 2013;5(1):1.CrossRef
Metadata
Title
Identification of a new alanine racemase in Salmonella Enteritidis and its contribution to pathogenesis
Authors
Shilpa Ray
Susmita Das
Pritam Kumar Panda
Mrutyunjay Suar
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Gut Pathogens / Issue 1/2018
Electronic ISSN: 1757-4749
DOI
https://doi.org/10.1186/s13099-018-0257-6

Other articles of this Issue 1/2018

Gut Pathogens 1/2018 Go to the issue

Research

Proliferation of enterotoxigenic Escherichia coli strain TW11681 in stools of experimentally infected human volunteers

Research

Genomic characterization of malonate positive Cronobacter sakazakii serotype O:2, sequence type 64 strains, isolated from clinical, food, and environment samples

Genome Report

Genome sequence of Shigella sonnei 4303

Research

Infectious bursal disease virus inoculation infection modifies Campylobacter jejuni–host interaction in broilers

Research

Impact of the introduction of a nucleic acid amplification test for Clostridium difficile diagnosis on stool rejection policies

Research

Gut colonization with vancomycin-resistant Enterococcus and risk for subsequent enteric infection

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits