Outer Membrane Profiles of Clonally Related Klebsiella pneumoniae

Insights

Multidrug-resistant Klebsiella pneumoniae poses a global threat. Reduced outer membrane permeability, often due to porin loss, significantly increases resistance to antibiotics like beta-lactams and fluoroquinolones.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Antimicrobial Resistance

Background:

  • Multiply-antibiotic resistant (multiresistant) Klebsiella pneumoniae strains, often carrying plasmids for extended-spectrum β-lactamases (ESBLs) or AmpC-type β-lactamases (ACTBLs), complicate treatment.
  • Global incidences of these resistant strains are increasing, with significant prevalence in the US and Europe, and higher rates in nosocomial outbreaks.
  • Resistance to fluoroquinolones is common in ESBL-producing strains, likely due to mutations affecting topoisomerase genes.

Purpose of the Study:

  • To investigate the mechanisms contributing to increased antibiotic resistance in Klebsiella pneumoniae.
  • To understand the role of outer membrane permeability and porin expression in antimicrobial resistance.
  • To identify genetic factors leading to reduced porin expression.

Main Methods:

  • Analysis of antibiotic resistance mechanisms in Klebsiella pneumoniae.
  • Examination of the correlation between ESBL/ACTBL production and reduced outer membrane permeability.
  • Investigation of mutations in porin genes leading to decreased porin expression.

Main Results:

  • Decreased outer membrane permeability, caused by loss or reduced expression of porins, significantly increases minimum inhibitory concentrations (MICs) for β-lactams and fluoroquinolones.
  • Reduced porin expression leads to decreased antibiotic influx and reduced access to intracellular targets.
  • Mutations in porin genes, including point mutations, deletions, and insertion sequences, are responsible for the reduction in porin expression.

Conclusions:

  • Reduced outer membrane permeability is a critical factor in the high-level resistance observed in multiresistant Klebsiella pneumoniae.
  • Targeting porin expression or function could be a strategy to overcome antibiotic resistance in these pathogens.
  • Understanding the genetic basis of porin loss is essential for developing new therapeutic approaches against Klebsiella pneumoniae infections.

Related Concept Videos

Bacterial Phylum Tenericutes01:24

Bacterial Phylum Tenericutes

The phylum Tenericutes, which includes the single class Mollicutes, comprises bacteria that lack cell walls. The term "Mollicutes" derives from the Latin word mollis, meaning "soft." These organisms are among the smallest known and are commonly referred to as mycoplasmas due to the prominence of the genus Mycoplasma, which includes well-known human pathogens. Despite their inability to stain gram-positively (a result of their lack of cell walls), mycoplasmas are phylogenetically related to the...
Bacterial Phylum Planctomycetes01:26

Bacterial Phylum Planctomycetes

Planctomycetes are a group of morphologically distinct bacteria predominantly classified into two orders: Planctomycetales and Brocadiales. These gram-negative bacteria exhibit unique features, including division by budding and the presence of stalks or appendages. Their cells are often found in rosette arrangements, and they are notable for possessing an S-layer in their cell envelope, which is relatively uncommon among bacteria. Additionally, Planctomycetes frequently exhibit intracellular...
Outer Layers of the Cell Envelope01:18

Outer Layers of the Cell Envelope

The outermost layers of prokaryotic cells play a critical role in their survival, virulence, and interaction with the environment. These layers, often composed of polysaccharides, polypeptides, or proteins, form protective and adhesive structures that vary in organization and function.Capsules and Slime LayersCapsules are highly organized, tightly bound layers that firmly attach to the bacterial cell wall. Capsules are usually made of polysaccharides, though some are made of polypeptides. These...
Atypical Pneumonia01:14

Atypical Pneumonia

Atypical pneumonia, often caused by Mycoplasma pneumoniae, is a form of pulmonary infection that differs from the classical presentation of bacterial pneumonia in both its cause and clinical symptoms. Mycoplasma pneumoniae is a pleomorphic bacterium notable for its lack of a rigid cell wall. This structural characteristic imparts resistance to beta-lactam antibiotics and significantly influences the bacterium’s behavior within the human host.Other pathogens responsible for the disease include...
Bacterial Phylum Proteobacteria01:26

Bacterial Phylum Proteobacteria

Proteobacteria, one of the largest and most diverse bacterial phyla, encompasses a wide range of Gram-negative bacteria distinguished by their outer membrane composed of lipopolysaccharides. These microorganisms exhibit various metabolic capabilities, including phototrophy, chemolithotrophy, and heterotrophy, and thrive in diverse environments from soil to aquatic systems and host-associated niches. The phylum is divided into six classes: Alphaproteobacteria, Betaproteobacteria,...
Archaeal Cell Wall01:29

Archaeal Cell Wall

Archaeal cell walls are structurally and compositionally distinct from their bacterial counterparts, lacking the characteristic peptidoglycan layer found in most bacteria. Instead, archaeal cell walls exhibit remarkable diversity, utilizing materials such as pseudomurein, polysaccharides, and proteins to construct their protective outer layers. This structural flexibility is closely tied to archaea's ecological adaptability.S-Layers: The Common Archaeal Cell WallThe S-layer is the most...