Antibiotics that Inhibit 30S or 50S Ribosomal Subunit Formation: Hygromycin B, Quinupristin-Dalfopristin and XRP 2868.

<p>Several antibiotics that prevent translation by binding to ribosomal subunits have been shown to also inhibit ribosomal subunit assembly (Champney and Tober 2003). The aminoglycoside hygromycin B was examined in <em>Escherichia coli</em> cells for inhibitory effects on translation and ribosomal subunit assembly. The streptogramin antibiotics quinupristin-dalfopristin and XRP 2868 (NXL 103) were examined for similar effects on these 2 cellular functions in antibiotic-resistant strains of <em>Haemophilus influenzae</em>, <em>Staphylococcus aureus</em>, and <em>Streptococcus pneumoniae</em>.</p><p>Pulse chase experiments were performed which verified slower rates of ribosomal subunit formation in drug treated cells. Hygromycin B exhibited a concentration dependent inhibitory effect on viable cell number, growth rate, protein synthesis and 30S and 50S subunit formation. 16S rRNA specific probes hybridized to rRNA fragments in cells treated with hygromycin B. RNase II and RNase III deficient strains of <em>E. coli</em> exhibited the most accumulation of 16S rRNA fragments upon treatment with hygromycin B. Examination of total RNA from treated cells showed an increase in RNA corresponding to precursor to the 16S rRNA while 16S rRNA decreased. There was also an increase in small fragment RNA. Hygromycin B was a more effective inhibitor of translation than ribosomal subunit formation in <em>E. coli</em>.</p><p>Two streptogramin antibiotics were compared for inhibitory effects in antibiotic-resistant <em>Haemophilus influenzae</em>, <em>Staphylococcus aureus</em>, and <em>Streptococcus pneumoniae</em>. IC₅₀ values for XRP 2868 were several fold lower than those of quinupristin-dalfopristin for inhibition of cell viability, protein synthesis, and ribosomal subunit formation. Both antibiotics revealed a concentration dependent inhibitory effect on cellular functions including 50S ribosomal subunit formation in the three organisms examined.</p><p>XRP 2868 inhibited both 50S ribosomal subunit assembly and translation. XRP 2868 was effective against MRSA and was a better inhibitor in each of the antibiotic resistant strains examined compared with quinupristin-dalfopristin.</p>

Name thesis:degree_name

PhD (Doctor of Philosophy)

Level thesis:degree_level

Dissertation - unrestricted

Discipline thesis:degree_discipline

Biomedical Sciences

Year dc:date.issued

2007

Author dc:creator

• McGaha, Susan Mabe

• Pathogenic bacteria
• Antibiotics
• Translational inhibitors
• Ribosomal subunit assembly
• Chemicals and Drugs
• Medicine and Health Sciences
• Polycyclic Compounds

Statement dc:rights

• Copyright by the authors.

Repository record dc:identifier

https://dc.etsu.edu/etd/2055

OAI identifier oai:identifier

oai:dc.etsu.edu:etd-3416