Robert Daum, M.D.

Bacterial Pathogenesis and Antibiotic Resistance

Research Summary

Dr. Daum’s NIH funded laboratory studies the pathogenesis of staphylococcal infections and molecular mechanisms of antimicrobial resistance. Specifically, the laboratory focuses on understanding the changes in the biochemistry of the cell wall of vancomycin-resistant Staphylococcus aureus strains. The first change occurring after exposure to vancomycin is resistance to endogenous endopeptidases, also called autolysins, enzymes intended to assist in cell division and replication. These enzymes are unable to lyse walls from at least some vancomycin-resistant cells. Paradoxically, these autolysins are produced in excessive quantities in these resistant strains. Taken together, these data suggest that cytoplasmic proteins are unable to anchor in the bacterial cell surface in these resistant strains. Genes up-regulated or down-regulated by vancomycin and related stress are also under study using microarray technology.

A separate project has begun to address the molecular biology of methicillin-resistant S. aureus (MRSA) strains now known to be circulating in the community. Until recently, these strains had been confined to the hospital environment. Initial data from the laboratory suggests that these isolates differed from their hospital circulating counterparts in that they are most often resistant only to methicillin alone and not to multiple antibiotics like hospital MRSA strains frequently are. These MRSA strains circulating in the community represent unique molecular clones inserted into the genome of classic "methicillin-susceptible backgrounds." Further work is in progress to further characterize the molecular epidemiology of these strains and to understand the molecular origins of this new resistant clone.

Selected Papers

Boyle-Vavra S, Berke SK, Daum RS. (2000). Reversion of glycopeptide resistance phenotype in Staphylococcus aureus clinical isolates Antimicrob Ag Chemother. 44:272-277.

Daum RS, Zenko CE, Given GZ, Ballanco GA, Parikh H, Vidor E, Liu X. (2000). Absence of a significant interaction between a DtaP/Hib combination vaccine and IPV. Pediatr Infect Dis J, 19:710-717.

Lin PL, Oram RJ, Lauderdale D. Dean R, Daum RS. (2000). Knowledge of CDC guidelines for the use of vancomycin in a large tertiary care children’s hospital. J Pediatr, 137:694-700.

Hussain FM, Boyle-Vavra S, Bethel CD, Daum RS. (2000). Current trends in community-acquired methicillin-resistant Staphylococcus aureus: at a tertiary care pediatric facility. Pediatr Infect Dis J, 19:1163-1166.

Boyle-Vavra S, Hahm J, Sibener SJ, Daum RS. (2000). Structural and Topological Differences between a Glycopeptide-Intermediate Clinical Strain and Glycopeptide-Susceptible Strains of Staphylococcus aureus Revealed by Atomic Force Microscopy. Antimicrob Ag Chemother, 44:3456-60.

Boyle-Vavra S, Labischinski H, Ebert CC, Ehlert K, Daum RS. (2001). A spectrum of changes occurs in peptidoglycan composition of glycopeptide-intermediate-resistant clinical Staphylococcus aureus isolates. Antimicrob Ag Chemother, 45:280-287.

Oram RJ, Daum RS, Seal JB, Lauderdale DA. (2001). Impact of recommendations to suspend the birth dose of hepatitis B virus vaccine in Cook County, Illinois. JAMA, 285:1874-1879.

Hussain FM, Boyle-Vavra S, Daum RS. (2001). Community-acquired methicillin-resistant Staphylococcus aureus colonization in healthy children attending an outpatient pediatric clinic. Pediatr Infect Dis J, 20:763-7.

Boyle-Vavra S, Carey R, Daum RS. (2001). Development of vancomycin and lysostaphin resistance in a methicillin-resistant Staphylococcus aureus isolate J Antimicrob Chemother, 48:617-625.

Daum RS, Zenko CE, Given GZ, Ballanco GA, Parikh H, Germino K. (2001). The magnitude of interference after DtaP/PRP-T vaccine is related to the number of doses administered. J Infect Dis, 184:1293-1299.

Ma XX, Ito T, Tiensasitorn C, Jamklang M, Chongtrakool P, Boyle-Vavra S, Daum RS, Hiramatsu K. (2002). A novel type of staphylococcal cassette chromosome mec (SCCmec) identified in community-acquired methicillin-resistant Staphylococcus aureus strains. Antimicrob Ag Chemother, 46:1147-1152.

Hussain FM, Boyle-Vavra S, Shete PB, Daum RS. (2002). Evidence for a continuum of decreased vancomycin susceptibility in unselected Staphylococcus aureus clinical isolates J Infect Dis 186:661-667.

Daum RS, Ito T, Hiramatsu K, Mongkolrattonathai K, Hussain F, Boyle-Vavra S. (2002). A novel staphylococcal chromosomal cassette containing mec is present in community acquired methicillin-resistant Staphylococcus aureus isolates in Chicago. J Infect Dis, 186:1344-1377.

Boyle-Vavra S, Yin S, Challapalli M, Daum RS. (2003). Transcriptional induction of the penicillin-binding protein 2 gene in Staphylococcus aureus by cell wall active antibiotics oxacillin and vancomycin. Antimicrob Ag Chemother, 47:1028-1036.

Cohen NJ, Lauderdale DS, Shete PB, Seal JB, Daum RS. (2003). Physician knowledge of catch-up regimens and contraindications for childhood immunizations. Pediatr, 111: 925-932.

Seal JB, Moreira B, Bethel CD, Daum RS. (2003). Antimicrobial resistance in Staphylococcus aureus at the University of Chicago Hospitals: 15-year longitudinal assessment in a large University-based hospital. Infect Control Hosp Epidem, 42:403-408.

Boyle-Vavra S, Challapalli M, Daum RS. (2003). Decreased autolytic capability in Staphylococcus aureus isolates selected in vancomycin precedes the vancomycin-intermediate resistance phenotype, Antimicrob Ag Chemother, 47:2036-2039.

Mongkolrattonathai K, Boyle-Vavra S, Kahana MD, Daum RS. (2003). Severe Staphylococcus aureus infection caused by clonally-related community-acquired methicillin-susceptible and methicillin resistant isolates Clin Inf Dis, 22:1050-1058.

Peev M, Weber SG, Daum RS, Garcia-Houchins S, Marcinak J. (2003). Disseminated vaccinia false alarm. Pediatr Inf Dis, 22:925-926.

Mongkolrattonathai K, Boyle-Vavra S, Murphy TV, Daum RS. (2004). Novel non mecA-containing SCC-Composite Island containing pbp4 and tagF genes in a commensal staphylococcal species:  a possible reservoir for antibiotic resistance islands in Staphylococcus aureus.  Antimicrob Ag Chemother  48:1823-1836.

Dominguez SR, Parrott JS, Lauderdale DS and Daum RS. (2004). On-time immunization rates among children entering Chicago Public Schools. Pediatr e741-747.

Dominguez SR and Daum RS. (2005). Physician knowledge adn perspective regarding influenza and influenza vaccination. Human Vaccines  1:xxx-yyy.

Adem PV, Montgomery CP, Husain AN, Koogler TK, Arangelovich V, Humilier M, Boyle-Vavra S and Daum RS.  (2005). Staphylococcus aureus sepsis and the Waterhouse-Friderichsen syndrome in children. N Eng J Med 353:1245-1251.

Boyle S, Ereshefsky B, Wang CC and Daum RS. (2005). A successful multi-resistant community associated MRSA lineage from Taipei, Taiwain that carries either a novel staphylococcal chromosomal cassette SCCmec type V_T or SCCmec type IV. J Clin Micro 42:4719-4730.

Yin S, Daum RS, Chaurushiya M and Boyle S. (2006). Characterization of the autoinducible VraSR two-component regulatory system and its role in transcriptional induction of pbb2 by ß-lactams and vancomycin using lacZ fusions on solid and liquid medium in Staphylococcus aureus. Antimicrob Ag Chemother 50:336-43.

Glikman D, Kahana M, Matushek S and Daum RS. (2006). Pneumonia and Empyema Caused by Penicillin-Resistant Neisseria meningitidis: A Case Report and Literature Review. Pediatrics 117e:1061-1066.

David MZ, Crawford SE, Boyle-Vavra S, Kim DC and Daum RS. (2006). Comparing Antibiotic Resistance among Community-Associated Methicillin-Resistant Staphylococcus aureus Isolates from Adults and Children. Emerg Inf Dis 12:631-637.

Boyle-Vavra S, Yin S and Daum RS. (2006). The VraS/VraR two-component regulatory system required for oxacillin resistance in community-acquired methicillin-resistant Staphylococcus aureus. FEMS Microbiol Lett, 262:163-171.

Maree C, Daum RS, Boyle-Vavra and Miller LG. (2007). A Rapid Increase in "Community-Associated" Methicillin-resistant Staphylococcus aureus Isolates Causing Healthcare-Associated Infections. Emerg Inf Dis 13:236-242.

Halperin SA, Vaudry W, Voucher FD, Mackintosh K, Waggener TB, Smith B for the Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC), Daum R, participating investigator. (2007). Is pertussis immune glovulin efficacious for the treatment of hopsitalized infants with pertussis? No answer yet. Pediatr Infect Dis J 26:79-81.

Glikman D, Nguyen-Dinh P, Roberts JM, Montgomery CP, Daum RS and Marcinak JF. (2007). Clinical malaria and sickle cell disease amont multiple family members in Chicago. Pedatr 120:e1-5.

Daum RS. (2007). The treatment of community-associated methicillin-resistant Staphylococcus aureus infections. N Eng J Med 357:380-90.