HWN Suggests

We need new antibiotics for Gram-negative, not Gram-positive bacteria

The threat from antibiotic resistance is more pink than purple. You probably need to be a microbiologist to get this: Gram-positive bacteria (such as MRSA and C. difficile) stain purple in the Gram stain, whereas Gram-negative bacteria (such as Klebsiella pneumoniae and Acinetobacter baumannii*) stain pink. All of the international concern surrounding antibiotic resistance from the WHO, CDC, PHE and others have focused our mind on one threat in particular: carbapenem-resistant Enterobacteriaceae (CRE). The Enterobacteriaceae family of bacteria are all Gram-negative, so we need to focus our drug discovery towards the Gram-negatives rather than the Gram-positives.

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 Aerobic Gram Negative Bacteria

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 Gram-Negative Bacterial Outer Membrane Molecular Complexity

When many of us think of a biological membrane on the molecular scale we picture a textbook image of a symmetric phospholipid bilayer that looks somewhat uncomplicated. The outer membrane of gram-negative bacteria is anything but symmetric and simple. We wanted the cover image to convey the molecular complexity and asymmetry of the outer membrane that these bacteria have as their first line of defense from their immediate environment.

 Hacking the Permeability Barrier of Gram-Negative Bacteria

Antibiotics save numerous lives. Although bacteria inevitably develop resistance to existing antibiotics thanks to natural evolution, humanity has been largely successful in keeping up with these evolving pathogens with the continuous discovery of new antibiotics─until recently. With the rapid rise of multidrug-resistant Gram-negative bacteria and a diminishing antibiotic pipeline, many fear that we are losing the tug-of-war between bacterial resistance and human innovation. Gram-negative bacteria account for the lion’s share of drug-resistant pathogens that cause life-threatening infections

Articles of Interest

Anaerobic Gram-Negative Bacteria: Role as a Reservoir of Antibiotic Resistance

Anaerobic Gram-negative bacteria (AGNB) play a significant role as both pathogens and essential members of the human microbiota. Despite their clinical importance, there remains limited understanding regarding their antimicrobial resistance (AMR) patterns. This knowledge gap poses challenges in effectively managing AGNB-associated infections, as empirical treatment approaches may not adequately address the evolving resistance landscape.

Classic Spotlight: Gram-Negative Bacteria Have Two Membranes

In a classic Journal of Bacteriology paper, Bladen and Mergenhagen showed clearly for the first time that unlike the cell envelopes of Gram-positive bacteria, which contain a thick peptidoglycan cell wall that surrounds a single membrane, the cell envelopes of Gram-negative bacteria are composed of three structural entities: an inner or cytoplasmic membrane, a thin, rigid cell wall, and an outer membrane.

Gram-negative Bacteria Infections in Healthcare Settings

Gram-negative bacteria cause infections including pneumonia, bloodstream infections, wound or surgical site infections, and meningitis in healthcare settings. Gram-negative bacteria are resistant to multiple drugs and are increasingly resistant to most available antibiotics. These bacteria have built-in abilities to find new ways to be resistant and can pass along genetic materials that allow other bacteria to become drug-resistant as well.

Gram-Negative Bacterial Infections: Research Priorities, Accomplishments, and Future Directions of the Antibacterial Resistance Leadership Group

The mission of the Gram-Negative Committee is to advance our knowledge of these challenging infections and implement studies to improve patient outcomes. Studies have fallen primarily into 2 broad categories: prospective cohort studies and interventional trials.

Gram-negative cell wall

The outer membrane shields bacteria and hinders some antibiotics. It contains Porin proteins that form pores for hydrophilic molecule diffusion and Lipopolysaccharides with a negative charge that helps maintain bacteria's shape, but also potentially causes toxic shock in infected hosts.

Gram‐Negative Anaerobes

Gram‐negative anaerobes represent an extremely diverse group of bacteria, so that generalization about their pathogenesis is difficult. Their study has been hindered by their requirement for anaerobic growth conditions, and often for specialized media; indeed, many species have never been successfully cultured.

Plasmids 101: Gram Negative and Positive Bacteria

In 1884, while studying infected lung tissue, a Danish biologist named Christian Gram realized that certain stains were retained only in some species of bacteria. The stain colored one type, Streptococcus pneumoniae, while the alcohol used in the staining process bleached another, Klebsiella pneumoniae. After realizing this was a repeatable phenomenon, Gram began using it as a classification system.

Resistance of Gram-Negative Bacteria to Current Antibacterial Agents and Approaches to Resolve It

Due to their distinctive structure, Gram-negative bacteria are more resistant than Gram-positive bacteria, and cause significant morbidity and mortality worldwide. Several strategies have been reported to fight and control resistant Gram-negative bacteria, like the development of antimicrobial auxiliary agents, structural modification of existing antibiotics, and research into and the study of chemical structures with new mechanisms of action and novel targets that resistant bacteria are sensitive to.

Scientists discover how antibiotics penetrate Gram-negative bacterial cell walls

Scientists have labored for decades to find antibiotics that work against Gram-negative bacteria, which cause some of the deadliest infections in hospital settings and are most likely to be resistant to treatment with existing antibiotics. In a study reported in the journal Chemical Science, researchers developed a new method to determine how antibiotics with specific chemical properties thread their way through tiny pores in the otherwise impenetrable cell envelopes of Gram-negative bacteria.

What Is Gram Negative Bacteria & Why Can It Cause So Many Diseases

Gram-negative bacteria have adapted to various environments and can be found in soil, water, plants, and animals, including humans. Their versatility and adaptability contribute to their ability to cause a multitude of diseases. Some notable examples of Gram-negative bacteria include Escherichia coli (E. coli), Salmonella spp., Pseudomonas aeruginosa, Klebsiella pneumoniae, and Neisseria gonorrhoeae.

What’s More Alarming? Gram Negative or Gram Positive Bacteria in Sepsis

After the introduction of antibiotics in early 1960s to 1980s it was seen that gram negative bacteria were the leading cause for causing sepsis as the antibiotics were showing more activity against the gram positive bacteria. In contrast the current situation showed increase in gram positive bacteria causing sepsis due to antimicrobial resistance.

‘Gram-Negative Bacteria Pose a Significant Scientific Challenge’

We face several hurdles in developing novel antibiotics to treat resistant infections. Gram-negative bacteria, such as Escherichia coli and Pseudomonas aeruginosa, pose a significant scientific challenge because their unique cell wall features make it difficult for antibiotics to work effectively.

Resources

StatPearls

Gram-negative bacteria (GNB) are among the world's most significant public health problems due to their high resistance to antibiotics. These microorganisms have significant clinical importance in hospitals because they often require patients to be in the intensive care unit (ICU), and patients are at high risk of morbidity and mortality. Two large groups, Enterobacteriaceae and the non-fermenters, are responsible for most clinical isolates; nevertheless, other clinically pertinent gram-negative organisms exist, including Neisseria, Haemophilus spp., Helicobacter pylori, and Chlamydia trachomatis.