{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T07:45:38Z","timestamp":1783755938075,"version":"3.55.0"},"reference-count":101,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T00:00:00Z","timestamp":1581379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Mouse models have been used to generate critical data for many infectious diseases. In the case of Burkholderia pseudomallei, mouse models have been invaluable for bacterial pathogenesis studies as well as for testing novel medical countermeasures including both vaccines and therapeutics. Mouse models of melioidosis have also provided a possible way forward to better understand the chronicity associated with this infection, as it appears that BALB\/c mice develop an acute infection with B. pseudomallei, whereas the C57BL\/6 model is potentially more suggestive of a chronic infection. Several unanswered questions, however, persist around this model. In particular, little attention has been paid to the effect of age or sex on the disease outcome in these animal models. In this report, we determined the LD50 of the B. pseudomallei K96243 strain in both female and male BALB\/c and C57BL\/6 mice in three distinct age groups. Our data demonstrated a modest increase in susceptibility associated with sex in this model, and we documented important histopathological differences associated with the reproductive systems of each sex. There was a statistically significant inverse correlation between age and susceptibility. The older mice, in most cases, were more susceptible to the infection. Additionally, our retrospective analyses suggested that the impact of animal supplier on disease outcome in mice may be minimal. These observations were consistent regardless of whether the mice were injected with bacteria intraperitoneally or if they were exposed to aerosolized bacteria. All of these factors should be considered when designing experiments using mouse models of melioidosis.<\/jats:p>","DOI":"10.3390\/pathogens9020113","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T11:45:30Z","timestamp":1581421530000},"page":"113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Impact of Age and Sex on Mouse Models of Melioidosis"],"prefix":"10.3390","volume":"9","author":[{"given":"Christopher P.","family":"Klimko","sequence":"first","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia R.","family":"Trevi\u00f1o","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia M.","family":"Moreau","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Pathology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Aponte Cuadrado","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua R.","family":"Meyer","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Fetterer","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Biostatistics Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Welkos","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia L.","family":"Worsham","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman","family":"Kreiselmeier","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Pathology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Soffler","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher K.","family":"Cote","sequence":"additional","affiliation":[{"name":"United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1128\/CMR.4.1.52","article-title":"Melioidosis: The tip of the iceberg?","volume":"4","author":"Dance","year":"1991","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0001-706X(99)00059-5","article-title":"Melioidosis as an emerging global problem","volume":"74","author":"Dance","year":"2000","journal-title":"Acta Trop."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15008","DOI":"10.1038\/nmicrobiol.2015.8","article-title":"Predicted global distribution of and burden of melioidosis","volume":"1","author":"Limmathurotsakul","year":"2016","journal-title":"Nat. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hassan, M.R., Pani, S.P., Peng, N.P., Voralu, K., Vijayalakshmi, N., Mehanderkar, R., Aziz, N.A., and Michael, E. (2010). Incidence, risk factors and clinical epidemiology of melioidosis: A complex socio-ecological emerging infectious disease in the Alor Setar region of Kedah, Malaysia. BMC Infect. Dis., 10.","DOI":"10.1186\/1471-2334-10-302"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3389\/fcimb.2012.00101","article-title":"Particle-size dependent effects in the BALB\/c murine model of inhalational melioidosis","volume":"2","author":"Thomas","year":"2012","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1111\/j.1365-2613.2012.00842.x","article-title":"Murine pulmonary infection and inflammation induced by inhalation of Burkholderia pseudomallei","volume":"93","author":"West","year":"2012","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"265","DOI":"10.3201\/eid2002.121891","article-title":"Melioidosis caused by Burkholderia pseudomallei in drinking water, Thailand, 2012","volume":"20","author":"Limmathurotsakul","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1086\/520223","article-title":"Risk factors for melioidosis and bacteremic melioidosis","volume":"29","author":"Suputtamongkol","year":"1999","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1007\/s40475-017-0131-5","article-title":"Animal models for melioidosis","volume":"4","author":"Amemiya","year":"2017","journal-title":"Curr. Trop. Med. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.3201\/eid0912.020750","article-title":"Intensity of rainfall and severity of melioidosis, Australia","volume":"9","author":"Currie","year":"2003","journal-title":"Emerg. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3201\/eid2101.140042","article-title":"Association of melioidosis incidence with rainfall and humidity, Singapore, 2003-2012","volume":"21","author":"Liu","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1093\/cid\/cir808","article-title":"Clinical features and epidemiology of melioidosis pneumonia: Results from a 21-year study and review of the literature","volume":"54","author":"Meumann","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1183\/09031936.03.00006203","article-title":"Melioidosis: An important cause of pneumonia in residents of and travellers returned from endemic regions","volume":"22","author":"Currie","year":"2003","journal-title":"Eur. Respir. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.ijantimicag.2014.01.005","article-title":"Treatment and prophylaxis of melioidosis","volume":"43","author":"Dance","year":"2014","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e141480","DOI":"10.3201\/eid2106.141480","article-title":"Consensus on the development of vaccines against naturally acquired melioidosis","volume":"21","author":"Limmathurotsakul","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Peacock, S.J., Limmathurotsakul, D., Lubell, Y., Koh, G.C., White, L.J., Day, N.P., and Titball, R.W. (2012). Melioidosis vaccines: A systematic review and appraisal of the potential to exploit biodefense vaccines for public health purposes. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001488"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"638","DOI":"10.3201\/eid1104.041051","article-title":"Route of infection in melioidosis","volume":"11","author":"Barnes","year":"2005","journal-title":"Emerg. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1046\/j.1440-1711.2001.01038.x","article-title":"Induction of multiple chemokine and colony-stimulating factor genes in experimental Burkholderia pseudomallei infection","volume":"79","author":"Barnes","year":"2001","journal-title":"Immunol. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.clim.2004.06.006","article-title":"Adaptive immunity in melioidosis: A possible role for T cells in determining outcome of infection with Burkholderia pseudomallei","volume":"113","author":"Barnes","year":"2004","journal-title":"Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1574-695X.2008.00389.x","article-title":"Susceptibility to Burkholderia pseudomallei is associated with host immune responses involving tumor necrosis factor receptor-1 (TNFR1) and TNF receptor-2 (TNFR2)","volume":"52","author":"Barnes","year":"2008","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1006\/mpat.1997.0179","article-title":"BALB\/c and C57Bl\/6 mice infected with virulent Burkholderia pseudomallei provide contrasting animal models for the acute and chronic forms of human melioidosis","volume":"24","author":"Leakey","year":"1998","journal-title":"Microb. Pathog."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bearss, J.J., Hunter, M., Dankmeyer, J.L., Fritts, K.A., Klimko, C.P., Weaver, C.H., Shoe, J.L., Quirk, A.V., Toothman, R.G., and Webster, W.M. (2017). Characterization of pathogenesis of and immune response to Burkholderia pseudomallei K96243 using both inhalational and intraperitoneal infection models in BALB\/c and C57BL\/6 mice. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172627"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1099\/jmm.0.47596-0","article-title":"Burkholderia pseudomallei aerosol infection results in differential inflammatory responses in BALB\/c and C57Bl\/6 mice","volume":"57","author":"Tan","year":"2008","journal-title":"J. Med. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Trevino, S.R., Klimko, C.P., Reed, M.C., Aponte-Cuadrado, M.J., Hunter, M., Shoe, J.L., Meyer, J.R., Dankmeyer, J.L., Biryukov, S.S., and Quirk, A.V. (2018). Disease progression in mice exposed to low-doses of aerosolized clinical isolates of Burkholderia pseudomallei. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0208277"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Welkos, S.L., Klimko, C.P., Kern, S.J., Bearss, J.J., Bozue, J., Bernhards, R.C., Trevin, S., Waag, D.M., Amemiya, K., and Worsham, P. (2015). Characterization of Burkholderia pseudomallei strains using a murine intraperitoneal infection model and in vitro macrophage assays. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124667"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.micpath.2015.07.004","article-title":"Comparison of the early host immune response to two widely diverse virulent strains of Burkholderia pseudomallei that cause acute and chronic infections in BALB\/c mice","volume":"86","author":"Amemiya","year":"2015","journal-title":"Microb. Pathog."},{"key":"ref_27","first-page":"120","article-title":"An objective approach for Burkholderia pseudomallei strain selection as challenge material for medical countermeasures efficacy testing","volume":"2","author":"Tuanyok","year":"2012","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1084\/jem.107.1.153","article-title":"Melioidosis: Pathogenesis and immunity in mice and hamsters. I. Studies with virulent strains of Malleomyces pseudomallei","volume":"107","author":"Dannenberg","year":"1958","journal-title":"J. Exp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s40121-015-0098-2","article-title":"Burkholderia Pseudomallei Causing Bone and Joint Infections: A Clinical Update","volume":"5","author":"Raja","year":"2016","journal-title":"Infect. Dis. Ther."},{"key":"ref_30","first-page":"649","article-title":"Rheumatological manifestations in patients with melioidosis","volume":"39","author":"Teparrakkul","year":"2008","journal-title":"Southeast Asian J. Trop. Med. Public Health"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Chen, P.S., Chen, Y.S., Lin, H.H., Liu, P.J., Ni, W.F., Hsueh, P.T., Liang, S.H., Chen, C., and Chen, Y.L. (2015). Airborne transmission of melioidosis to humans from environmental aerosols contaminated with B. pseudomallei. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003834"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1365-2613.2008.00619.x","article-title":"Experimental acute respiratory Burkholderia pseudomallei infection in BALB\/c mice","volume":"90","author":"Lever","year":"2009","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.1038\/srep04305","article-title":"Comparative Burkholderia pseudomallei natural history virulence studies using an aerosol murine model of infection","volume":"4","author":"Massey","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Challacombe, J.F., Stubben, C.J., Klimko, C.P., Welkos, S.L., Kern, S.J., Bozue, J.A., Worsham, P.L., Cote, C.K., and Wolfe, D.L. (2014). Interrogation of the Burkholderia pseudomallei Genome to Address Differential Virulence among Isolates. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115951"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.1128\/IAI.67.6.2891-2900.1999","article-title":"Characterization of a murine model of melioidosis: Comparison of different strains of mice","volume":"67","author":"Hoppe","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.cellimm.2007.09.006","article-title":"Stress hormones and immune function","volume":"252","author":"Glaser","year":"2008","journal-title":"Cell. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"292","DOI":"10.4269\/ajtmh.15-0567","article-title":"Sri Lankan National Melioidosis surveillance program uncovers a nationwide distribution of invasive melioidosis","volume":"94","author":"Corea","year":"2016","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1111\/j.1365-3156.2004.01328.x","article-title":"Melioidosis epidemiology and risk factors from a prospective whole-population study in northern Australia","volume":"9","author":"Currie","year":"2004","journal-title":"Trop. Med. Int. Health"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"983","DOI":"10.4269\/ajtmh.13-0286","article-title":"Prevalence of melioidosis in patients with suspected pulmonary tuberculosis and sputum smear negative for acid-fast bacilli in northeast Thailand","volume":"89","author":"Suntornsut","year":"2013","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/nri.2016.90","article-title":"Sex differences in immune responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Chirakul, S., Bartpho, T., Wongsurawat, T., Taweechaisupapong, S., Karoonutaisiri, N., Talaat, A.M., Wongratanacheewin, S., Ernst, R.K., and Sermswan, R.W. (2014). Characterization of BPSS1521 (bprD), a regulator of Burkholderia pseudomallei virulence gene expression in the mouse model. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104313"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1038\/srep01146","article-title":"Efficacy of post exposure administration of doxycycline in a murine model of inhalational melioidosis","volume":"3","author":"Gelhaus","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1128\/IAI.68.4.2034-2042.2000","article-title":"Cytokine gene expression in innately susceptible BALB\/c mice and relatively resistant C57BL\/6 mice during infection with virulent Burkholderia pseudomallei","volume":"68","author":"Ulett","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wiersinga, W.J., Calandra, T., Kager, L.M., van der Windt, G.J., Roger, T., le Roy, D., Florquin, S., Peacock, S.J., Sweep, F.C., and van der Poll, T. (2010). Expression and function of macrophage migration inhibitory factor (MIF) in melioidosis. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000605"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1128\/IAI.00930-12","article-title":"Impaired early cytokine responses at the site of infection in a murine model of type 2 diabetes and melioidosis comorbidity","volume":"81","author":"Hodgson","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1128\/CVI.05545-11","article-title":"Cationic liposomes extend the immunostimulatory effect of CpG oligodeoxynucleotide against Burkholderia pseudomallei infection in BALB\/c mice","volume":"19","author":"Puangpetch","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_47","first-page":"551","article-title":"Glycogen synthase kinase-3beta inhibition improved survivability of mice infected with Burkholderia pseudomallei","volume":"29","author":"Tay","year":"2012","journal-title":"Trop Biomed."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1164\/rccm.201307-1344OC","article-title":"Endogenous alpha2-antiplasmin is protective during severe gram-negative sepsis (melioidosis)","volume":"188","author":"Kager","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e221","DOI":"10.1097\/CCM.0000000000000134","article-title":"Mice lacking the lectin-like domain of thrombomodulin are protected against melioidosis","volume":"42","author":"Kager","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1128\/IAI.05534-11","article-title":"Expression and function of transforming growth factor beta in melioidosis","volume":"80","author":"Weehuizen","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9015","DOI":"10.1038\/s41598-017-09373-0","article-title":"Host-adaptation of Burkholderia pseudomallei alters metabolism and virulence: A global proteome analysis","volume":"7","author":"Mariappan","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Weehuizen, T.A., Prior, J.L., van der Vaart, T.W., Ngugi, S.A., Nepogodiev, S.A., Field, R.A., Kager, L.M., van\u2019t Veer, C., de Vos, A.F., and Wiersinga, W.J. (2015). Differential Toll-like receptor-signalling of Burkholderia pseudomallei lipopolysaccharide in murine and human models. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0145397"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/2049-632X.12172","article-title":"Genetic control of weight loss during pneumonic Burkholderia pseudomallei infection","volume":"71","author":"Emery","year":"2014","journal-title":"Pathog. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Kager, L.M., Wiersinga, W.J., Roelofs, J.J., de Boer, O.J., Weiler, H., van\u2019t Veer, C., and van der Poll, T. (2014). A thrombomodulin mutation that impairs active protein C generation is detrimental in severe pneumonia-derived gram-negative sepsis (melioidosis). PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002819"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1128\/CMR.11.2.231","article-title":"Natural pathogens of laboratory mice, rats, and rabbits and their effects on research","volume":"11","author":"Baker","year":"1998","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Kline, K.A., Schwartz, D.J., Gilbert, N.M., and Lewis, A.L. (2014). Impact of host age and parity on susceptibility to severe urinary tract infection in a murine model. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097798"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"S74","DOI":"10.1086\/315915","article-title":"Antioxidants, cytokines, and influenza infection in aged mice and elderly humans","volume":"182","author":"Han","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"358","DOI":"10.14336\/AD.2017.0701","article-title":"Aged mice are more resistant to influenza virus infection due to reduced inflammation and lung pathology","volume":"9","author":"Lu","year":"2018","journal-title":"Aging Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5203","DOI":"10.1128\/IAI.69.8.5203-5206.2001","article-title":"Susceptibility of mice to vaginal infection with Chlamydia trachomatis mouse pneumonitis is dependent on the age of the animal","volume":"69","author":"Pal","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Puchta, A., Naidoo, A., Verschoor, C.P., Loukov, D., Thevaranjan, N., Mandur, T.S., Nguyen, P.S., Jordana, M., Loeb, M., and Xing, Z. (2016). TNF drives monocyte dysfunction with age and results in impaired anti-pneumococcal immunity. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005368"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1177\/153537020222700208","article-title":"An aged mouse model for RSV infection and diminished CD8+ CTL response","volume":"227","author":"Zhang","year":"2002","journal-title":"Exp. Biol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1128\/JCM.43.2.970-972.2005","article-title":"Cutaneous melioidosis in a man who was taken as a prisoner of war by the Japanese during World War II","volume":"43","author":"Ngauy","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Limmathurotsakul, D., Chaowagul, W., Chantratita, N., Wuthiekanun, V., Biaklang, M., Tumapa, S., White, N.J., Day, N.P., and Peacock, S.J. (2008). A simple scoring system to differentiate between relapse and re-infection in patients with recurrent melioidosis. PLoS Negl. Trop. Dis., 2.","DOI":"10.1371\/journal.pntd.0000327"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Jenjaroen, K., Chumseng, S., Sumonwiriya, M., Ariyaprasert, P., Chantratita, N., Sunyakumthorn, P., Hongsuwan, M., Wuthiekanun, V., Fletcher, H.A., and Teparrukkul, P. (2015). T-cell responses are associated with survival in acute melioidosis patients. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0004152"},{"key":"ref_65","unstructured":"(2020, January 29). Of mice and men\u2014are mice relevant models for human disease?. Available online: https:\/\/ec.europa.eu\/research\/health\/pdf\/summary-report-25082010_en.pdf."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1242\/dmm.024547","article-title":"Using the mouse to model human disease: Increasing validity and reproducibility","volume":"9","author":"Justice","year":"2016","journal-title":"Dis. Models Mech."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s40139-015-0086-y","article-title":"Mouse models as predictors of human responses: Evolutionary medicine","volume":"3","author":"Uhl","year":"2015","journal-title":"Curr. Pathobiol. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"227","DOI":"10.4269\/ajtmh.17-0633","article-title":"Prostatic abscess due to Burkholderia pseudomallei: Facilitating diagnosis to optimize management","volume":"98","author":"Kozlowska","year":"2018","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.juro.2009.04.010","article-title":"Prostatic abscess due to Burkholderia pseudomallei: 81 cases from a 19-year prospective melioidosis study","volume":"182","author":"Morse","year":"2009","journal-title":"J. Urol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Currie, B.J., Ward, L., and Cheng, A.C. (2010). The epidemiology and clinical spectrum of melioidosis: 540 cases from the 20 year Darwin prospective study. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000900"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.idcr.2018.01.001","article-title":"An unusual case of primary melioidotic prostatic abscess complicated by perianal abscess","volume":"11","author":"Chee","year":"2018","journal-title":"IDCases"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Nernsai, P., Sophonsritsuk, A., Lertvikool, S., Jinawath, A., and Chitasombat, M.N. (2018). A case report of Tubo-ovarian abscess caused by Burkholderia pseudomallei. BMC Infect. Dis., 18.","DOI":"10.1186\/s12879-018-2986-z"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Barthold, S.W., Griffey, S.M., and Percy, D.H. (2016). Pathology of Laboratory Rodents and Rabbits, Wiley-Blackwell. [4th ed.].","DOI":"10.1002\/9781118924051"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/ab.10035","article-title":"Strain-specific aggressive behavior of male mice submitted to different husbandry procedures","volume":"29","author":"Kruitwagen","year":"2003","journal-title":"Aggress. Behav."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Kappel, S., Hawkins, P., and Mendl, M.T. (2017). To group or not to group? Good practice for housing male laboratory mice. Animals, 7.","DOI":"10.20944\/preprints201710.0150.v1"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.coi.2009.07.001","article-title":"Age-associated declines in immune system development and function: Causes, consequences, and reversal","volume":"21","author":"Dorshkind","year":"2009","journal-title":"Curr. Opin. Immunol."},{"key":"ref_77","first-page":"525","article-title":"Immune responses in aged mice","volume":"5","author":"Kishimoto","year":"1969","journal-title":"Clin. Exp. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1172\/JCI64096","article-title":"Causes, consequences, and reversal of immune system aging","volume":"123","author":"Dorshkind","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_79","first-page":"512","article-title":"Immunity, cancer and aging: Lessons from mouse models","volume":"2","author":"Myers","year":"2011","journal-title":"Aging Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1099\/jmm.0.013250-0","article-title":"Effect of age on susceptibility to Salmonella Typhimurium infection in C57BL\/6 mice","volume":"58","author":"Ren","year":"2009","journal-title":"J. Med. Microbiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1093\/infdis\/jix414","article-title":"Innate immune response and outcome of Clostridium difficile infection are dependent on fecal bacterial composition in the aged host","volume":"217","author":"Shin","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1093\/infdis\/jix417","article-title":"Clostridium difficile, Aging, and the gut: Can microbiome rejuvenation keep us young and healthy?","volume":"217","author":"Fischer","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5708","DOI":"10.1016\/j.vaccine.2019.07.103","article-title":"Robust Th1 cellular and humoral responses generated by the Yersinia pestis rF1-V subunit vaccine formulated to contain an agonist of the CD137 pathway do not translate into increased protection against pneumonic plague","volume":"37","author":"Bowen","year":"2019","journal-title":"Vaccine"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4438","DOI":"10.1128\/IAI.05267-11","article-title":"Resistance to Yersinia pestis infection decreases with age in B10.T(6R) mice","volume":"79","author":"Lambert","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/427606a","article-title":"Evolutionary genetics: CCR5 mutation and plague protection","volume":"427","author":"Mecsas","year":"2004","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.exger.2009.10.004","article-title":"Aged mice display an altered pulmonary host response to Francisella tularensis live vaccine strain (LVS) infections","volume":"45","author":"Mares","year":"2010","journal-title":"Exp. Gerontol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4801","DOI":"10.1128\/IAI.72.8.4801-4809.2004","article-title":"Murine model of pulmonary anthrax: Kinetics of dissemination, histopathology, and mouse strain susceptibility","volume":"72","author":"Lyons","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"12694","DOI":"10.1128\/JVI.02282-12","article-title":"Aged mice exhibit a severely diminished CD8 T cell response following respiratory syncytial virus infection","volume":"87","author":"Fulton","year":"2013","journal-title":"J. Virol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Wong, T.M., Boyapalle, S., Sampayo, V., Nguyen, H.D., Bedi, R., Kamath, S.G., Moore, M.L., Mohapatra, S., and Mohapatra, S.S. (2014). Respiratory syncytial virus (RSV) infection in elderly mice results in altered antiviral gene expression and enhanced pathology. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088764"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1038\/s41385-019-0171-3","article-title":"Sex-associated TSLP-induced immune alterations following early-life RSV infection leads to enhanced allergic disease","volume":"12","author":"Malinczak","year":"2019","journal-title":"Mucosal Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1084\/jem.20100282","article-title":"Age-dependent susceptibility to a viral disease due to decreased natural killer cell numbers and trafficking","volume":"207","author":"Fang","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_92","first-page":"789","article-title":"Age-associated variability in susceptibility of Swiss Webster mice to MPV and other excluded murine pathogens","volume":"51","author":"Grove","year":"2012","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_93","first-page":"797","article-title":"Transmission of mouse parvovirus to neonatoal mice","volume":"51","author":"Compton","year":"2012","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.virol.2015.03.020","article-title":"Limited susceptibility of mice to Usutu virus (USUV) infection and induction of flavivirus cross-protective immunity","volume":"482","author":"Blazquez","year":"2015","journal-title":"Virology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"eaar2749","DOI":"10.1126\/scitranslmed.aar2749","article-title":"Acute and chronic neurological consequences of early-life Zika virus infection in mice","volume":"10","author":"Frost","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1099\/vir.0.82359-0","article-title":"Early restriction of alphavirus replication and dissemination contributes to age-dependent attenuation of systemic hyperinflammatory disease","volume":"88","author":"Ryman","year":"2007","journal-title":"J. Gen. Virol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3468","DOI":"10.3390\/v4123468","article-title":"Development of a murine model for aerosolized ebolavirus infection using a panel of recombinant inbred mice","volume":"4","author":"Zumbrun","year":"2012","journal-title":"Viruses"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"919","DOI":"10.3201\/eid2505.180928","article-title":"Formaldehyde and glutaraldehyde inactivation of bacterial Tier 1 select agents in tissues","volume":"25","author":"Chua","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"ref_99","first-page":"865","article-title":"Bacterial filamentation of Yersinia pestis by beta-lactam antibiotics in experimentally infected mice","volume":"121","author":"Davis","year":"1997","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1198\/tast.2010.08130","article-title":"A geometric comparison of the delta and Fieller confidence intervals","volume":"64","author":"Hirschberg","year":"2010","journal-title":"Am. Stat."},{"key":"ref_101","unstructured":"Finney, D.J. (1971). Probit Analysis, Cambridge University Press. [3rd ed.]."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/2\/113\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:56:56Z","timestamp":1760173016000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/2\/113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,11]]},"references-count":101,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["pathogens9020113"],"URL":"https:\/\/doi.org\/10.3390\/pathogens9020113","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,11]]}}}