Plasmids are extra mini-chromosomes that are present in many bacteria. They carry information that enables their hosts to survive and prosper in hostile environments. Plasmids are able to spread rapidly between bacteria, ensuring that the information they carry is rapidly disseminated throughout bacterial populations. Many plasmids carry information that increases the virulence of their host bacteria, because it adds to their repertoire of toxins and other adjuncts to invasiveness and colonisati ....Plasmids are extra mini-chromosomes that are present in many bacteria. They carry information that enables their hosts to survive and prosper in hostile environments. Plasmids are able to spread rapidly between bacteria, ensuring that the information they carry is rapidly disseminated throughout bacterial populations. Many plasmids carry information that increases the virulence of their host bacteria, because it adds to their repertoire of toxins and other adjuncts to invasiveness and colonisation, or enables them to survive in the presence of antibiotics. The emergence of multi-drug resistant bacteria and the rapid spread of the ability of bacteria to withstand most antibiotics available to date were mediated by plasmids. Plasmids also carry information that ensures their own survival. The consequence of this is that their bacterial hosts retain the plasmids, even when it is no longer beneficial to do so. For example, plasmids carrying information for resistance to antibiotics are not lost when their bacterial hosts grow in the absence of antibiotics. This is because plasmids have control systems, which ensure that on the one hand, replication of the plasmid keeps pace with the replication of its host, and on the other hand that the plasmid does not produce so many copies of itself that it overwhelms its host. This project examines the intricate regulatory system that a group of antibiotic-resistance plasmids uses to ensure that on average each plasmid molecule is replicated once per bacterial cell cycle. This system uses an antisense RNA, a tertiary RNA structure (pseudoknot) that acts as a translational switch, and a protein that interacts with different sequences on the plasmid to initiate replication. Detailed knowledge of the processes underlying this complex system is required if we are to develop new treatments that will lead to elimination of antibiotic-resistance and virulence-contributing plasmids from populations of pathogenic bacteria.Read moreRead less
Plasmids are additional mini-chromosomes carried by many bacteria. They carry information that enables their hosts to prosper in otherwise hostile environments. Plasmids spread rapidly between bacteria, efficiently disseminating plasmid-borne information throughout bacterial populations. Many plasmids carry information that increases the virulence of their host. The emergence of multi-drug resistant bacteria and the rapid spread of the information enabling bacteria to withstand most antibiotics ....Plasmids are additional mini-chromosomes carried by many bacteria. They carry information that enables their hosts to prosper in otherwise hostile environments. Plasmids spread rapidly between bacteria, efficiently disseminating plasmid-borne information throughout bacterial populations. Many plasmids carry information that increases the virulence of their host. The emergence of multi-drug resistant bacteria and the rapid spread of the information enabling bacteria to withstand most antibiotics available today, were mediated by plasmids. Plasmids also carry information that ensures their own survival. Consequently, their hosts retain the plasmids even when it is no longer beneficial for them to do so. For example, plasmids mediating resistance to antibiotics are not lost when bacterial hosts are grown in the absence of those antibiotics. That is because plasmids have control systems, which ensure both that replication of the plasmid keeps pace with that of its host, and that the plasmid does not produce so many copies of itself that it overwhelms its host or places it at a competitive disadvantage amongst other bacteria. This project examines the intricate regulatory system that enables two groups of antibiotic-resistance plasmids to ensure that, on average, each plasmid molecule is replicated once per bacterial cell cycle. This system uses a tertiary RNA structure as a molecular switch, an antisense RNA as the regulator of this switch, and a protein that interacts with DNA sequences on the plasmid and with a bacterial protein, to initiate replication. Information gained from studies of plasmid systems is essential to the development of treatments for the elimination of antibiotic-resistance and virulence-contributing plasmids from populations of pathogenic bacteria. Antisense RNAs are not only a powerful research tool, but are also being developed for therapeutic use. Understanding how these RNAs interact with their targets will increase their effectiveness.Read moreRead less
Analysis And Regulation Of Leptospiral Virulence Factors.
Funder
National Health and Medical Research Council
Funding Amount
$630,465.00
Summary
Leptospirosis is a globally important infectious disease caused by Leptospira spp. This project aims to identify and characterise factors which play a role in disease development by knocking out genes, then investigating the impact on overall gene-protein expression in the mutant strain and its ability to cause disease. This will allow us to gain insights on mechanisms by which Leptospira spp. cause disease, leading to development of better methods of disease control and prevention.
Molecular Characterization Of E. Coli That Cause Urinary Tract Infection
Funder
National Health and Medical Research Council
Funding Amount
$387,114.00
Summary
The long term goals of the proposed research are to understand the processes by which uropathogenic Escherichia coli (UPEC) cause acute, recurrent and chronic infections and to identify new UPEC targets for therapeutic intervention. Urinary tract infections (UTI) are among the most common infectious diseases of humans and a major cause of morbidity and mortality. In the USA, UTI accounts for more than 1 million hospitalizations and $1.6 billion in medical expenditures each year. It is estimated ....The long term goals of the proposed research are to understand the processes by which uropathogenic Escherichia coli (UPEC) cause acute, recurrent and chronic infections and to identify new UPEC targets for therapeutic intervention. Urinary tract infections (UTI) are among the most common infectious diseases of humans and a major cause of morbidity and mortality. In the USA, UTI accounts for more than 1 million hospitalizations and $1.6 billion in medical expenditures each year. It is estimated that one in four women and one in twenty men will develop a UTI in their lifetime. The recurrence rate is high and no treatment other than antibiotics (often inefficient) is currently available. UPEC are the primary cause of UTI. In the last grant period, we focused on the molecular interplay that exists between different surface adhesins of UPEC. We succeeded in demonstrating functional interference between adhesins, motility organelles, aggregation factors and the capsule. We also discovered and partially characterized several novel UPEC adhesins that may play a role in pathogenesis. We established two novel technology sets: a mouse model of ascending UTI and the flow chamber biofilm model. In the next grant period, we will build on these concepts and experimental systems to gain a deeper understanding of the molecular mechanisms underlying UPEC virulence. We will characterize the role of several novel UPEC surface proteins in cell adhesin, aggregation, biofilm formation and colonization of the mouse urinary tract. We will employ an integrated approach that combines a powerful bacterial genetic system, a biofilm model, a mouse UTI model, microscopy and tissue culture systems to reveal the cellular, molecular, and structural basis for the pathogenesis of UTI. The work will facilitate the development of new vaccine approaches to prevent UTI, such as novel mechanisms for strain attenuation and vaccine design. The burden of UTI disease demands such research endeavours.Read moreRead less