Methylobacterium mesophilicum

Updated : November 16, 2023

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Methylobacterium mesophilicum is primarily a soil-dwelling bacterium with the potential to cause opportunistic infections, particularly in individuals with compromised immune systems. Environmental contamination and exposure, often stemming from tap water, have been associated with its transmission.

Reported cases of M. mesophilicum infections have been relatively scarce and primarily documented in developed countries like the United States, Canada, France, and Japan. These infections tend to occur in patients with underlying conditions, including cancer, organ transplantation, or HIV infection.  

The most frequently encountered clinical manifestations of M. mesophilicum infections include bacteremia, peritonitis, and pneumonia. However, the true prevalence of M. mesophilicum infections remains to be determined, as routine testing and reporting in most clinical laboratories are rare.

Emerging research suggests these infections might be more widespread than previously recognized, especially in hospitals where tap water is a potential contamination source. For instance, a study conducted in France identified M. mesophilicum as the most commonly isolated, pink-pigmented bacterium in hospital water samples. It was also detected in blood cultures from 11 patients over four years.  

Although no documented outbreaks of M. mesophilicum infection have been reported to date, there exists a potential risk of nosocomial transmission via contaminated medical devices or equipment that come into contact with tap water.

An illustrative case from Japan recounted an instance where a patient developed peritonitis attributed to M. mesophilicum after undergoing continuous ambulatory peritoneal dialysis that employed tap water as the diluent.

While comprehensive estimates of M. mesophilicum infection incidence, mortality, and morbidity are lacking, some studies have indicated a high case-fatality rate, ranging from 18% to 50%, contingent on the infection site and its severity.  

 

Classification and Structure: 

Kingdom: Bacteria 

Phylum: Pseudomonadota 

Class: Alphaproteobacteria 

Order: Hyphomicrobiales 

Family: Methylobacteriaceae 

Genus: Methylobacterium 

Species: M. mesophilicum  

Methylobacterium mesophilicum is classified as a gram-negative bacterium. Its cell envelope comprises a thin peptidoglycan layer and an outer membrane. Notably, it exhibits a distinctive pink pigmentation attributed to carotenoid pigments within its cell membrane. After extended incubation, it can give rise to coral-colored colonies when cultured on agar plates.  

This bacterium is a straight or slightly curved rod, displaying a non-motile and non-spore-forming nature. It typically measures approximately 0.5-0.8 µm in width and 1.5-3.0 µm in length. 

M. mesophilicum is classified as a methylotrophic bacterium, which signifies its ability to utilize methanol and other one-carbon compounds as its primary carbon and energy sources. As an aerobic bacterium, it relies on oxygen for its growth and metabolic processes.

 

Methylobacterium mesophilicum, a relatively rare and opportunistic pathogen with a propensity to infect immunocompromised individuals, exhibits several potential virulence factors. Regarding virulence genes, it harbors crucial elements like “mxaF,” responsible for encoding MxaF-type methanol dehydrogenase or MDH, which is pivotal role in methanol oxidation & electron transfer.

Another significant gene is “crtE,” responsible for carotenoid synthesis, protecting against oxidative stress and UV radiation. The “eps” gene cluster also contributes to extracellular polysaccharide production, potentially aiding surface adherence and immune evasion.  

M. mesophilicum features “XoxF,” an alternative MDH that utilizes lanthanum as a cofactor, enabling growth on methanol under these conditions. “PQQ-ADH” enzymes are also present in the oxidation of various alcohols. M. mesophilicum DSM 1708T, the type strain of this species, has a fascinating history, having been originally isolated from English soil and initially classified as Pseudomonas mesophilica.

M. mesophilicum displays lipopolysaccharide (LPS) and outer membrane proteins (Omp) as potential stimulators of the innate immune system. The extracellular polysaccharides produced by this pathogen can act as antigens, influencing host immunity.

 

The pathogenesis of Methylobacterium mesophilicum presents challenges in understanding, primarily due to its status as a rare and opportunistic pathogen. This bacterium can find its way into healthcare settings, contaminating medical devices and equipment that have contact with environmental sources, including catheters, dialysis machines, or dental units.

Subsequently, it enters the human body through various routes, such as wounds, mucous membranes, or intravenous lines, giving rise to infections. Once inside the host, M. mesophilicum can adhere to and invade various human cells, including epithelial cells, endothelial cells, and macrophages.

Additionally, it demonstrates the ability to form biofilms on surfaces, potentially bolstering its resistance to antibiotics and evading host immune defenses. Infections attributed to M. mesophilicum are often associated with using contaminated medical devices, notably central venous catheters or peritoneal dialysis catheters.

These devices can serve as conduits for introducing the bacterium into critical sites such as the bloodstream or the peritoneal cavity, thereby initiating the infection. 

 

Human host defenses against Methylobacterium mesophilicum encompass a multi-tiered continuum of protection. Initially, nonspecific barriers serve as the primary defense, shielding the host from the diverse array of bacteria encountered in the natural environment. These barriers act as physical and chemical deterrents, preventing the entry of potential pathogens.  

The innate immune system detects the M. mesophilicum in the bloodstream through pattern recognition receptors (PRRs). These receptors identify specific molecular patterns on the bacterium’s surface, initiating antimicrobial defenses and activating the adaptive immune system.  

The immune system orchestrates a robust neutrophilic response, often resulting in the formation of pus. Individuals with loss-of-function mutations in constitutive immune mechanisms may exhibit increased susceptibility to specific infections or infections in particular organs.

This susceptibility extends beyond acute to chronic and latent infections, sometimes accompanied by heightened inflammation. Such deficiencies can lead to the accumulation of pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns, and homeostasis-altering processes, ultimately resulting in pathological inflammation. 

Clinical manifestations of Methylobacterium mesophilicum infection encompass several potential presentations, often dependent on the site of infection:  

Pneumonia:M. mesophilicum infections may also manifest as pneumonia, characterized by lung inflammation. Symptoms of M. mesophilicum pneumonia include cough, chest pain, shortness of breath, and fever. This presentation has been reported in patients with underlying conditions such as cystic fibrosis or those who have undergone lung transplantation.  

Bacteremia:M. mesophilicum infection can lead to bacteremia, characterized by bacteria in the bloodstream. This condition typically manifests with fever and chills and, in severe cases, may progress to septic shock. Bacteremia has been observed in patients with central venous catheters, peritoneal dialysis catheters, or a history of intravenous drug use.  

Peritonitis: Infections with Me. mesophilicum can result in peritonitis, the inflammation of the peritoneum, the membrane lining the abdominal cavity, and its organs. This condition presents with symptoms like abdominal pain, tenderness, distension, and fluid accumulation within the abdominal cavity. Patients undergoing continuous ambulatory peritoneal dialysis are particularly susceptible to M. mesophilicum peritonitis. 

 

Diagnosing Methylobacterium mesophilicum infection can be challenging due to its rarity and fastidious nature. However, several diagnostic tests can be employed to identify this bacterium: 

Culture test: The most common method involves isolating and identifying M. mesophilicum from clinical samples. This method requires special media and conditions, such as methanol or nutrient agar supplemented with yeast extract and vitamin B12. Incubation at 30°C for 3-7 days is necessary.

Typically, colonies of M. mesophilicum are pink-pigmented and may develop a coral hue with extended incubation. Selective media such as chocolate agar is often employed for culture. Initially, the organism typically produces white colonies on chocolate agar. However, within 48 hours of incubation, these colonies tend to develop a distinctive pink pigmentation. 

Biochemical Tests: These tests assess the metabolic reactions of M. mesophilicum to various substrates and indicators, including: 

  • Oxidase Test:M. mesophilicum is oxidase positive, producing a dark blue or purple color when exposed to an oxidase reagent. 
  • Urease Test: It is urease positive, resulting in a pink or magenta color when grown on a urea-containing medium. 
  • Catalase Test:M. mesophilicum is weakly catalase positive, generating a weak or delayed bubbling when exposed to hydrogen peroxide. 
  • Motility Test:M. mesophilicum is motile, exhibiting a diffuse growth or turbidity when inoculated into a motility medium. It possesses a single polar flagellum. 
  • Oxidative-Fermentative (OF) Test: This test confirms that M. mesophilicum is an obligate aerobe, requiring oxygen for growth and metabolism. It does not produce acid on OF media with 1% glucose. 

Molecular Tests: Molecular methods offer higher sensitivity and specificity and include: 

  • 16S rRNA Gene Sequencing: This method relies on the unique 16S ribosomal RNA gene sequence of M. mesophilicum, which can be compared with reference databases to confirm its identity. 
  • Multilocus Sequence Analysis (MLSA): MLSA identifies bacteria based on the sequence of several housekeeping genes, offering enhanced discrimination for closely related species. 
  • Average Nucleotide Identity (ANI): ANI measures genomic similarity by comparing the percentage of identical nucleotides in bacterial genomes, aiding in reliable species delineation. 
  • Regular monitoring of tap water quality is essential to detect potential contamination. Using filters or purifiers can reduce the risk of exposure to M. mesophilicum in tap water. Maintenance and periodic replacement of filters are crucial to prevent biofilm formation and bacterial growth, ensuring water safety for consumption. 
  • Medical devices or equipment that contact with tap water, such as catheters, dialysis machines, or dental units, should undergo thorough and regular disinfection. The disinfection methods used should be effective against biofilm-forming bacteria. 
  • Regular monitoring of water quality and microbiological contamination within healthcare facilities, especially in units caring for immunocompromised patients, is vital. M. mesophilicum can be isolated from various sources, including tap water, endoscopes, dental units, and blood purification units. Timely sampling and testing of these sources can help identify and eliminate potential reservoirs and transmission routes. 
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Methylobacterium mesophilicum

Updated : November 16, 2023

Mail Whatsapp PDF Image



Methylobacterium mesophilicum is primarily a soil-dwelling bacterium with the potential to cause opportunistic infections, particularly in individuals with compromised immune systems. Environmental contamination and exposure, often stemming from tap water, have been associated with its transmission.

Reported cases of M. mesophilicum infections have been relatively scarce and primarily documented in developed countries like the United States, Canada, France, and Japan. These infections tend to occur in patients with underlying conditions, including cancer, organ transplantation, or HIV infection.  

The most frequently encountered clinical manifestations of M. mesophilicum infections include bacteremia, peritonitis, and pneumonia. However, the true prevalence of M. mesophilicum infections remains to be determined, as routine testing and reporting in most clinical laboratories are rare.

Emerging research suggests these infections might be more widespread than previously recognized, especially in hospitals where tap water is a potential contamination source. For instance, a study conducted in France identified M. mesophilicum as the most commonly isolated, pink-pigmented bacterium in hospital water samples. It was also detected in blood cultures from 11 patients over four years.  

Although no documented outbreaks of M. mesophilicum infection have been reported to date, there exists a potential risk of nosocomial transmission via contaminated medical devices or equipment that come into contact with tap water.

An illustrative case from Japan recounted an instance where a patient developed peritonitis attributed to M. mesophilicum after undergoing continuous ambulatory peritoneal dialysis that employed tap water as the diluent.

While comprehensive estimates of M. mesophilicum infection incidence, mortality, and morbidity are lacking, some studies have indicated a high case-fatality rate, ranging from 18% to 50%, contingent on the infection site and its severity.  

 

Classification and Structure: 

Kingdom: Bacteria 

Phylum: Pseudomonadota 

Class: Alphaproteobacteria 

Order: Hyphomicrobiales 

Family: Methylobacteriaceae 

Genus: Methylobacterium 

Species: M. mesophilicum  

Methylobacterium mesophilicum is classified as a gram-negative bacterium. Its cell envelope comprises a thin peptidoglycan layer and an outer membrane. Notably, it exhibits a distinctive pink pigmentation attributed to carotenoid pigments within its cell membrane. After extended incubation, it can give rise to coral-colored colonies when cultured on agar plates.  

This bacterium is a straight or slightly curved rod, displaying a non-motile and non-spore-forming nature. It typically measures approximately 0.5-0.8 µm in width and 1.5-3.0 µm in length. 

M. mesophilicum is classified as a methylotrophic bacterium, which signifies its ability to utilize methanol and other one-carbon compounds as its primary carbon and energy sources. As an aerobic bacterium, it relies on oxygen for its growth and metabolic processes.

 

Methylobacterium mesophilicum, a relatively rare and opportunistic pathogen with a propensity to infect immunocompromised individuals, exhibits several potential virulence factors. Regarding virulence genes, it harbors crucial elements like “mxaF,” responsible for encoding MxaF-type methanol dehydrogenase or MDH, which is pivotal role in methanol oxidation & electron transfer.

Another significant gene is “crtE,” responsible for carotenoid synthesis, protecting against oxidative stress and UV radiation. The “eps” gene cluster also contributes to extracellular polysaccharide production, potentially aiding surface adherence and immune evasion.  

M. mesophilicum features “XoxF,” an alternative MDH that utilizes lanthanum as a cofactor, enabling growth on methanol under these conditions. “PQQ-ADH” enzymes are also present in the oxidation of various alcohols. M. mesophilicum DSM 1708T, the type strain of this species, has a fascinating history, having been originally isolated from English soil and initially classified as Pseudomonas mesophilica.

M. mesophilicum displays lipopolysaccharide (LPS) and outer membrane proteins (Omp) as potential stimulators of the innate immune system. The extracellular polysaccharides produced by this pathogen can act as antigens, influencing host immunity.

 

The pathogenesis of Methylobacterium mesophilicum presents challenges in understanding, primarily due to its status as a rare and opportunistic pathogen. This bacterium can find its way into healthcare settings, contaminating medical devices and equipment that have contact with environmental sources, including catheters, dialysis machines, or dental units.

Subsequently, it enters the human body through various routes, such as wounds, mucous membranes, or intravenous lines, giving rise to infections. Once inside the host, M. mesophilicum can adhere to and invade various human cells, including epithelial cells, endothelial cells, and macrophages.

Additionally, it demonstrates the ability to form biofilms on surfaces, potentially bolstering its resistance to antibiotics and evading host immune defenses. Infections attributed to M. mesophilicum are often associated with using contaminated medical devices, notably central venous catheters or peritoneal dialysis catheters.

These devices can serve as conduits for introducing the bacterium into critical sites such as the bloodstream or the peritoneal cavity, thereby initiating the infection. 

 

Human host defenses against Methylobacterium mesophilicum encompass a multi-tiered continuum of protection. Initially, nonspecific barriers serve as the primary defense, shielding the host from the diverse array of bacteria encountered in the natural environment. These barriers act as physical and chemical deterrents, preventing the entry of potential pathogens.  

The innate immune system detects the M. mesophilicum in the bloodstream through pattern recognition receptors (PRRs). These receptors identify specific molecular patterns on the bacterium’s surface, initiating antimicrobial defenses and activating the adaptive immune system.  

The immune system orchestrates a robust neutrophilic response, often resulting in the formation of pus. Individuals with loss-of-function mutations in constitutive immune mechanisms may exhibit increased susceptibility to specific infections or infections in particular organs.

This susceptibility extends beyond acute to chronic and latent infections, sometimes accompanied by heightened inflammation. Such deficiencies can lead to the accumulation of pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns, and homeostasis-altering processes, ultimately resulting in pathological inflammation. 

Clinical manifestations of Methylobacterium mesophilicum infection encompass several potential presentations, often dependent on the site of infection:  

Pneumonia:M. mesophilicum infections may also manifest as pneumonia, characterized by lung inflammation. Symptoms of M. mesophilicum pneumonia include cough, chest pain, shortness of breath, and fever. This presentation has been reported in patients with underlying conditions such as cystic fibrosis or those who have undergone lung transplantation.  

Bacteremia:M. mesophilicum infection can lead to bacteremia, characterized by bacteria in the bloodstream. This condition typically manifests with fever and chills and, in severe cases, may progress to septic shock. Bacteremia has been observed in patients with central venous catheters, peritoneal dialysis catheters, or a history of intravenous drug use.  

Peritonitis: Infections with Me. mesophilicum can result in peritonitis, the inflammation of the peritoneum, the membrane lining the abdominal cavity, and its organs. This condition presents with symptoms like abdominal pain, tenderness, distension, and fluid accumulation within the abdominal cavity. Patients undergoing continuous ambulatory peritoneal dialysis are particularly susceptible to M. mesophilicum peritonitis. 

 

Diagnosing Methylobacterium mesophilicum infection can be challenging due to its rarity and fastidious nature. However, several diagnostic tests can be employed to identify this bacterium: 

Culture test: The most common method involves isolating and identifying M. mesophilicum from clinical samples. This method requires special media and conditions, such as methanol or nutrient agar supplemented with yeast extract and vitamin B12. Incubation at 30°C for 3-7 days is necessary.

Typically, colonies of M. mesophilicum are pink-pigmented and may develop a coral hue with extended incubation. Selective media such as chocolate agar is often employed for culture. Initially, the organism typically produces white colonies on chocolate agar. However, within 48 hours of incubation, these colonies tend to develop a distinctive pink pigmentation. 

Biochemical Tests: These tests assess the metabolic reactions of M. mesophilicum to various substrates and indicators, including: 

  • Oxidase Test:M. mesophilicum is oxidase positive, producing a dark blue or purple color when exposed to an oxidase reagent. 
  • Urease Test: It is urease positive, resulting in a pink or magenta color when grown on a urea-containing medium. 
  • Catalase Test:M. mesophilicum is weakly catalase positive, generating a weak or delayed bubbling when exposed to hydrogen peroxide. 
  • Motility Test:M. mesophilicum is motile, exhibiting a diffuse growth or turbidity when inoculated into a motility medium. It possesses a single polar flagellum. 
  • Oxidative-Fermentative (OF) Test: This test confirms that M. mesophilicum is an obligate aerobe, requiring oxygen for growth and metabolism. It does not produce acid on OF media with 1% glucose. 

Molecular Tests: Molecular methods offer higher sensitivity and specificity and include: 

  • 16S rRNA Gene Sequencing: This method relies on the unique 16S ribosomal RNA gene sequence of M. mesophilicum, which can be compared with reference databases to confirm its identity. 
  • Multilocus Sequence Analysis (MLSA): MLSA identifies bacteria based on the sequence of several housekeeping genes, offering enhanced discrimination for closely related species. 
  • Average Nucleotide Identity (ANI): ANI measures genomic similarity by comparing the percentage of identical nucleotides in bacterial genomes, aiding in reliable species delineation. 
  • Regular monitoring of tap water quality is essential to detect potential contamination. Using filters or purifiers can reduce the risk of exposure to M. mesophilicum in tap water. Maintenance and periodic replacement of filters are crucial to prevent biofilm formation and bacterial growth, ensuring water safety for consumption. 
  • Medical devices or equipment that contact with tap water, such as catheters, dialysis machines, or dental units, should undergo thorough and regular disinfection. The disinfection methods used should be effective against biofilm-forming bacteria. 
  • Regular monitoring of water quality and microbiological contamination within healthcare facilities, especially in units caring for immunocompromised patients, is vital. M. mesophilicum can be isolated from various sources, including tap water, endoscopes, dental units, and blood purification units. Timely sampling and testing of these sources can help identify and eliminate potential reservoirs and transmission routes. 

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