Thermal Control of Dairy Bacteriophage White Paper Thermal Control of Dairy Bacteriophage TABLE OF CONTENTS EXECUTIVE SUMMARY......................................................................................................3 INTRODUCTION TO SPX FLOW TECHNOLOGY ..................................................3 Vision and commitment...................................................................................................... 3 Customer focus .................................................................................................................. 3 INTRODUCTION TO BACTERIOPHAGE ...................................................................4 MORPHOLOGY AND TAXONOMY.................................................................................4 LIFE CYCLES.............................................................................................................................6 BACTERIOPHAGE IN THE DAIRY................................................................................8 CONTROLLING BACTERIOPHAGE IN THE DAIRY ENVIRONMENT........8 GENERAL RECOMMENDATIONS................................................................................8 KILLING PHAGE BY HEAT TREATMENT...................................................................8 LOGARITHMIC REDUCTION............................................................................................8 PHAGE LETHAL TIME AND TEMPERATURE COMBINATIONS ACHIEVED WITH SPX FLOW TECHNOLOGIES....................................................9 THERMAL TREATMENT OF WHEY PROTEIN CONCENTRATES AND CONTROL OF BACTERIOPHAGE USING APV LEANCREME™ TECHNOLOGY....................................................................................................................... 11 REFERENCES....................................................................................................................... 12 2 2 2 0 0 6 -X X-X X- 2 01 2 - G B Thermal Control of Dairy Bacteriophage Executive Summary Introduction to SPX Flow Technology The APV LeanCreme™ technology involves the addition of VI S ION AN D COM M ITM E NT microparticulated whey protein concentrate to be added to SPX's Flow Technology segment designs, manufactures cheese milk as a means of increasing cheese yield and/or and markets process engineering and automation to reduce the fat content of the cheese whithout comprim- solutions to the dairy, food, beverage, marine, ising product taste, flavour and texture. pharmaceutical and personal care industries through its This white paper describes bacteriophage and explains global operations. how to reduce the possibility of phage attack on the cheese We are committed to helping our customers all over the starter culture whilst maintaining the essential functional- world to improve the performance and profitability of ity of APV LeanCreme™. It is demonstrated that the time/ their manufacturing plant and processes. We achieve this temperature conditions applied during the microparticula- by offering a wide range of products and solutions from tion process are sufficient to destroy most of the less heat engineered components to design of complete process resistant bacteriophage encountered in dairies. However, plants supported by world leading applications and some high heat resistant strains being able to survive tem- development expertise. peratures of 115°C. If there is a concern for these specific strains then LeanCreme has to be combined with non-heated based methods to prevent phage contamination. We continue to help our customers optimise the performance and profitability of their plant throughout its service life with support services tailored to their individual As a matter of fact, it is not recommended to apply needs through a coordinated customer service and spare temperatures above 85ºC to 90ºC in order to destroy all parts network. phage as it will cause excessive denaturation of the microparticulated whey protein with the result that less protein will be incorporated into the cheese. Whatever heat treatment is applied it is a general recommandation to combine the heat treatment with e.g. culture rotation and chemical cleaning to limit the presence of phage. It is not just a matter of heat treatment. By having a low growth of phage as a starting point for a stream means C U S TO M E R F O C U S Founded in 1910, APV, an SPX Brand, has pioneered groundbreaking technologies over more than a century, setting the standards of the modern processing industry. Continuous research and development based on customer needs and an ability to visualise future process requirements drives continued mutual growth. that a gentler heat treatment is required (lower logarithmic reduction). The quality of the final product in terms of microbiology, taste and texture can hereby be preserved. 3 Thermal Control of Dairy Bacteriophage Introduction to bacteriophage Fermentation defects or failures in products like cheese and fermented milk products can result in changes in texture, gas formation and flavour of the products. Fermentation failures can, among others issues, be caused by bacteriophage contamination and therefore understanding the role of bacteriophage and what can be done to avoid them, is important. One way of controlling bacteriophage is by thermal treatment. M O R P H O L O GY A N D TA XO N O M Y Bakthrion (bakterion) = bacteria Fagoz (phágos) = to eat Bacteriophage is a virus that replicates itself using hosting bacteria. The term is commonly used in its shortened form, phage. Phage comes from the Greek work “phagein” and means “to Bacteriophage are a natural part of our surroundings and are eat” - bacteriophage can literally be translated to “to eat bacte- amongst the most common organisms on Earth, e.g. 10 million ria” (http://en.wikipedia.org/wiki/Bacteriophage). bacteriophage exist in one single millilitre of sea water and exist in general in the biosphere and therefore also in the air (http:// en.Wikipedia.org/wiki/Bacteriophage). This partly explains why bacteriophage cannot be fully avoided. In the case of dairies some species of bacteriophage are not wanted due to risk of fermentation failures. However, a lot can be done to limit the occurrence. Below is an electron micrograph showing a number of bacteriophage invading a bacterium. F I G . 2 A : A N E L E CT R O N M I C R O G R A P H ( H T T P : / / W W W. M A N S F I E L D . O H I O - S TAT E . E D U / ~ S A B E D O N / B E G _ P H A G E _ I M A G E S . H T M A N D H T T P : / / E N.W I K I P E D IA.O R G /W I K I / BACTE R I O P HAG E) H EAD CONTA I N I N G D N A COLLAR S H E AT H B AS E P L AT E TA I L F I B R E S F I G . 1 : E L E C T R O N M I C R O G R A P H S H OW I N G B ACT E R I O P H AG E I N VA D - F I G . 2 B : A S C H E M AT I C I L L U ST R AT I O N O F B A CT E R I O P H A G E , ( H T T P : / / I N G A B ACT E R I U M , ( H T T P : / / E N . W I K I P E D I A . O R G / W I K I / B ACT E R I O - W W W. M A N S F I E L D . O H I O - S TAT E . E D U / ~ S A B E D O N / B E G _ P H A G E _ I M A G - P HAG E) E S.HTM AN D HTTP:// E N.W I K I P E D IA.O R G /W I K I / BACTE R I O P HAG E) 4 2 2 0 0 6 - 0 3 - 1 1 - 2 01 2 - G B Thermal Control of Dairy Bacteriophage Phage infect bacteria and the properties of the bacteria can All phage have a head which contains the DNA or RNA genetic be changed or even destroyed. These changes are often not material. Many but not all phage have tails. The base plate and harmful and may even be beneficial. However, in fermented tail fibres are involved in binding of the phage to the bacterial dairy products like cheese and yoghurt where starter cultures cell. Bacteriophage are often much smaller than bacteria – usu- are used, such changes are not wanted since the fermentation ally between 20 to 200 nm (Madigan et al., 2000). process can be retarded or completely stopped. For practical reasons, bacteriophage are classified according to Bacteriophage come in many different sizes and shapes. The the International Committee on Taxonomy of Viruses (ICTV). As basic structure is illustrated in the electron micrograph and can be seen in Table 1 below, the morphology determines the schematic drawing on figs. 2a and 2b. classification, e.g. if a phage has tail or not. B R A D L E Y ( 19 67 ) NAM E M O R P H O LO GY A C K E R M A N N & D U B OW ( 19 87 ) NAM E M O R P H O LO GY I C T V ( 19 8 2 ) FA M I LY GENUS A A1, A2, A3 M YOV I R I D A E - B B1, B2, B3 S I P H OV I R I D A E - C C1, C2, C3 P O D OVI R I DAE - D1 M I C R OV I R I D A E M I C R OVI R U S D2 N OT C L A S S I F I E D - D3 C O RTI C IVI R I DAE C O RTI C OVI R U S D4 T E CT I V I R I D A E T E CT I V I R U S E1 LEVIVI R I DAE LEVIVI R US E2 CYST I V I R I D A E CYSTO V I R U S D E F1 F I N OVI R U S I N OV I R I D A E F2 - G P L E C TO V I R U S P L A S M AV I R I D A E P L A S M AV I R U S TA B L E 1 : C O M PA R I S O N O F P H AG E C L AS S I F I CAT I O N BY B R A D L E Y ( 1 9 67 ) , BY A C K E R M A N N A N D D U B O W ( 1 9 87 ) A N D BY T H E I N T E R N AT I O N A L C O M M I T T E E O N TA X O N O M Y O F V I R U S E S ( I CT V, 1 9 8 2 ) 2 2 0 0 6 - 0 3 - 1 1 - 2 01 2 - G B 5 Thermal Control of Dairy Bacteriophage F I G 4 : . S C H E M AT I C S H O W I N G T H E P R O C E S S O F B A C T E R I O P H A G E H O ST I N G B A CT E R I A , H T T P : / / W W W. M A N S F I E L D . O H I O - S TAT E . E D U / ~ S A B E D O N / B E G _ P H A G E _ I MAG E S.HTM F I G . 3 . LY T I C A N D LYS O G E N I C B ACT E R I O P H AG E I N F E CT I O N . H T T P : / / E N . W I K I P E D I A . O R G / W I K I / LY T I C _ CYC L E L I F E CYC L E S (attaching) before it penetrates the tail into the host cell. Finally The process of “infection” is where a virus genome (e.g. DNA) the DNA of the phage is injected into the cell. is introduced into a host cell and reproduces (Madigan et al., 2000). Some bacteriophage can propagate by both the lytic and the lysogenic cycle, and are normally referred to as “temperate” Phage can reproduce via two different life cycles - the lytic and phage. In the lysogenic cycle, the host and phage form a the lysogenic cycle. See fig. 3. symbiosis. The phage genome is integrated into the host Some phage replicate via the lytic cycle and are normally referred to as “virulent ”. In the lytic life cycle, the phage open (lyse) the bacterial cell resulting in destruction. When virulent bacteriophage infect bacteria, sub-units of phage are synthesised, assemble and finally mature phage is released. The host cell is killed. The released phage are now ready to infect a new bacterium. Fig. 4 illustrates the process of the DNA injection in detail. First step is the landing of the phage onto the living cell. The landing can only occur if specific bacteria cell surface components, called receptors, match the tail fibres of the phage. There is a high specificity in this landing step like the match of a key and lock. One way for the bacteria to defend it self is to have no recep- genome and replicated with it. At some point in time, phage is released and enters into the lytic phase. The majority of Lactococcus lactis phage strains are lysogenic. The period from landing of phage to assembly and release of phage is called the latent period. The burst size is the number of phage released from each bacterium. This number can vary from 200 to less than 10 and is phage specific. The consequence of infected bacteria in a fermentation process can be slow acidification or stagnancy. In practice, the fermentation period has to be extended to reach the normal fermentation pH. The fermentation curves differ greatly if the burst size is high. On the other hand, if the burst size is low the fermentation curve may not differ significantly at first sight. Schematic illustration of the influence of burst size on the fermentation curve can be seen in the graphs. tors. If the receptors exist, the second step is the phage pinning 6 2 2 0 0 6 - 0 3 - 1 1 - 2 01 2 - G B Thermal Control of Dairy Bacteriophage F I G . 5 . E X A M P L E S O F C O M P U T E R S I M U L AT E D F E R M E N TAT I O N C U R V E S W I T H B A C T E R I A I N F E C T E D BY P H A G E W I T H B U R S T S I Z E S O F 2 0 A N D 10 0 (I DF NO. 308, 1995) As can be seen the number of bacteria decreases as the the starting number of phage is higher with the result that the number of bacteriophage increases. In these examples a burst fermentation curve stagnates. size of 20 results in prolonged fermentation time and burst size of 100 results in stagnation of pH. In the graphs in fig. 6, the burst size is just 7, which is low. At Bacteriophage tend to mutate spontaneously in response to changes in environment which can make them aggressive e.g. if starter culture rotation is not done. day 1, the fermentation seems normal. However, at day two F I G . 6 . C O M P U T E R S I M U L AT E D E F F E CT O F T I M E O N F E R M E N TAT I O N C U R V E S W I T H B A C T E R I A I N F E C T E D BY P H A G E W I T H A B U R S T S I Z E O F 7 ( I D F NO. 308, 1995) 2 2 0 0 6 - 0 3 - 1 1 - 2 01 2 - G B 7 Thermal Control of Dairy Bacteriophage BAC T E R I O P H AG E I N T H E DA I RY The presence of phage cannot be avoided but a lot can be done It has been estimated that dairies experience phage-induced to limit their presence. Below are general recommendations as fermentation failure in 0.1. – 10% of the batches. 95% of the to how to avoid bacteriophage contamination. phage problems in dairies are caused by the phage species of 936, P335 and C2. The most important and most widespread phage to Lactococcus lactis is P008. It is therefore the most investigated phage for this bacterium. The latency period and burst size are dependant on the incubation conditions. It has been found that under optimal conditions, the latency period is 24 to 37 min and the burst size is 7 to 22. In other words one P008 phage usually takes 30 minutes to replicate it self to 7 to 22 phage. This is a rather quick replication and is even faster than the host bacterium itself (Müller-Merbach 2007). Phage P008 is accepted as the official type phage for Lactococcus lactis phage species 936 representing the Siphoviridae G E N E R A L R E C O M M E N D AT I O N S • Culture rotation and use of highly concentrated direct starters (deep frozen or spray dried) • Apply an efficient heat treatment to the whey • Hygienic design of plant, e.g. avoid dead ends and reflux • Handling of whey and whey plant. Personnel working with whey should preferably not work with the starter culture and should not be in contact with the fermentation process. The fermentation process should, as far as possible be a closed process • Sufficient and regular cleaning, and disinfection with appropriate agents • Handling of air with use of high efficiency particulate air family of morphotype B1. P008 is approved by the Lactococcal filtration of incoming air and slight overpressure in processing and Streptococcal Phage Study Group, Bacterial Virus Subcom- rooms mittee, ICTV as the test phage in the European standard CEN/ TC 216/WG3 N 42: "Chemical disinfectants and antiseptics - Quantitative suspension test for the evaluation of virucidal activity of chemical disinfectants and antiseptics used in food, industrial, domestic, and institutional areas. • Break the reincorporation of by products into the milk regularly (e.g. whey and whey cream) K I L L I N G P H AG E BY H E AT T R E AT M E N T Killing and inactivation of bacteriophage infecting lactic acid bacteria has been of interest ever since phage were observed P1532 and P680 are the most heat resistant Lactococcal bac- and caused fermentation failures in milk. Literature information teriophage in milk systems investigated until now. Both of them has been controversial. However, newly extensive investigations belong to the Lactococcus lactis phage and the 936 species provide data to calculate process conditions that assure adequate (Müller-Merbach 2007). P1532 is extremely heat stable but also phage destruction to prevent fermentation failure. Whey can carry very rare. P1532 was detected in 0.7 % of investigated dairies up to 107 to 109 PFU/ml (Atamer el., 2009). Plaque Forming and is therefore extremely rare (Dogan et al., 2008). Units is a measure of the number of particles capable of forming Phage of the host Lactococcus lactis and Lactobacillus helveticus bacteria is known to be relatively stable compared to Lactobacillus delbrueckii and Streptococcus thermophilus phage. C O N T R O L L I N G BACT E R I O P H A G E I N T H E DA I RY E N V I R O N M E N T plaques per unit volume. It is a functional measurement rather than a measurement of the absolute quantity of phage. LOGAR ITH M I C R E D U CTI ON When micro-organisms are exposed to heat treatment, not all of them are killed at once. Phage enter the dairy via raw milk and whey. Some phage may However, in a given period of time a certain number are killed survive normal pasteurisation. Inside the dairy they are mainly whilst the remainder survives. If the surviving micro-organisms spread in the whey and recirculation of whey cream can poten- are once more exposed to the temperature treatment for the tially accelerate phage contamination problems. Reincorporation same period of time an equal proportion will be killed. On this of milk components must therefore, be handled under carefully basis, the lethal effect of sterilisation can be expressed math- controlled conditions. ematically as a logarithmic function having a first order kinetic. 8 2 2 0 0 6 - 0 3 - 1 1 - 2 01 2 - G B Thermal Control of Dairy Bacteriophage K*t = log N/Nt P H AG E L E T H A L T I M E A N D T E M P E R AT U R E C O M B I N AT I O N S AC H I E V E D W I T H S P X F LOW Where TE CH N OLOG I E S N = number of micro-organisms/bacteriophage In terms of phage risk, thermal treatment has the potential Nt = number of micro-organisms/bacteriophage present after a given time of treatment (t) to increase the safety of fermentation process. To determine optimal thermal treatment for a specific case it should be more effective than a normal pasteurisation but less destructive than K = constant that required for heat sterilisation. t = time of treatment The time temperature graph on the next page shows the so A logarithmic function can never reach zero, which means that called “lines of equal effect”. Lines of equal effect indicate 100 % elimination is impossible to achieve. Therefore the more combinations of time and temperature which lead to an equal workable concept of “sterilising effect” or “commercial sterility” effect of a reaction, e.g. an equal degree of phage inactivation is commonly applied. Table 2 shows an example of the influence or destruction of vitamin B1 (thiamine). Lines for the widespread of log reductions on survivors and killed phage. In this case the phage P008 and for the rare and extremely heat stable phage starting point is 100,000,000 (108) of phage. Raw milk might P1532 are given for log 9 reductions. In an investigation 0.7 have up to 103 PFU/ml. of samples from dairies were infected by P1532, so this is an Having a log reduction of 8 in this example gives 1 surviving phage out of 100,000,000. LO G R E D UCTION extremely rare phage (Dogan et al., 2008). Log 9 reduction is usually sufficient for concentrated milk components like whey protein concentrates (WPC’s) as WPC often has a higher S U R V I VO R S K I L L E D P H AG E U N IT OF TI M E level of bacteriophage than raw milk. Referring to table of log reduction it can be seen that the initial level of bacteriophage is important in determining the heat treatment that is given. 0 100.000.000 0 0 1 10.000.000 90.000.000 1 A general rule is to aim for a threshold of 1 PFU/ml on the basis 2 1.000.000 99.000.000 2 3 100.000 99.900.000 3 of the rate of phage reproduction. Assuming a reproduction 4 10.000 99.990.000 4 5 1.000 99.999.000 5 6 100 99.999.900 6 7 10 99.999.990 7 8 1 99.999.999 8 According to fig. 7, a 9-log reduction of the commonly found 9 0,1 99.999.999,9 9 10 0,01 99.999.999,99 10 phage P008 can be reached with temperature and time com- 11 0,001 99.999.999,999 11 12 0,0001 99.999.999,9999 12 13 0,00001 99.999.999,99999 13 TA B L E 2 . OV E R V I E W O F L I N K B E T W E E N LO G R E D U CT I O N , S U R V I V - according to phage P008 and optimum growth conditions, the phage titre will increase from 1 PFU/ml to a maximum of 107 PFU/ml during a 4 hour long fermentation. This should not put the fermentation at risk yet (Müller-Merbach, 2007). bination ranging from 70°C for 20 min to 90°C for 1 sec. and therefore pasteurisation is normally not sufficient. A log reduction of 9 is a high reduction Other milk components are also affected by a given temperature I N G P H AG E , K I L L E D P H AG E A N D U N I T O F T I M E F O R A C O N S TA N T and time as can be seen in the temperature time graph. The H E AT T R E AT M E N T T E M P E R AT U R E . challenge is to find the optimal time and temperature for a given process without destroying the end product taste and texture. As an example, the loss of vitamin B1 and denaturation of whey proteins can be mentioned. Vitamin B1 is normally not wanted to 2 2 0 0 6 - 0 3 - 1 1 - 2 01 2 - G B 9 Thermal Control of Dairy Bacteriophage LTLT ge an ch ur olo fc n tructio Pha 1D .B cti tru on og og ,3l ,9l milk milk es 2 in 2 in 153 153 Vit ge P ge P HTST Destru Ultra high temperature heating (UHT) f Patho ction o 10 Pasteurisation Heating time or equivalent heating time in seconds e des Pha Typical LeanCreme Region 100 go nin gin Be Spor k, 9 log k, 3 log mil P008 in Phage mil P008 in Phage 1000 Sterilisation gens High temperature heating 1 60 2.9 2.8 72 84 2.6 2.7 Temperature 1/T in 10-³ K-¹ 97 112 2.5 2.4 2.3 127 144 162 Temperature in °C F I G . 7. T E M P E R AT U R E T I M E G R A P H S O F M I L K I N D I CAT I N G L I N E S O F E Q U A L E F F E C T I N C L U D I N G I N A C T I VAT I O N O F T H E M O S T C O M M O N B A C T E R I O P H A G E P 0 0 8 , T H E E X T R E M E LY R A R E A N D H E AT R E S I STA N T B ACT E R I O P H A G E P 1 5 3 2 . R E G I O N O F T Y P I CA L L E A N C R E M E T E M P E R AT U R E A N D T I M E C O M B I N AT I O N S A R E S H O W E D . ( K E S S L E R , 2 0 0 2 A N D ATA M E R E L A L . , 2 0 0 9 , M O D I F I E D ) 10 2 2 0 0 6 - 0 3 - 1 1 - 2 01 2 - G B Thermal Control of Dairy Bacteriophage be lost, since it is an important vitamin. In general, short time and cheese, yoghurt, ice crème among others). This high function- higher temperature is most gentle to the product compared to ality is indeed based on a loose and open structure enabling long time and lower temperature. active sites of the protein to interact with the components in the T H E R M A L T R E AT M E N T O F W H E Y P R OT E I N milk (Spiegel, 1999). C O N C E N T R AT E S A N D C O N T R O L O F In conclusion the optimal heat treatment and shear can create BACT E R I O P H AG E U S I N G A P V L E A N C R E M E ™ an extremely high quality of microparticulate can be produced to T E C H N O LO GY boost the sensory and structural quality of the end product, while The APV LeanCreme™ process is a thermal treatment of WPC at the same time preventing contamination of the most common (whey protein concentrate) with scrape surface heat exchang- bacteriophage encountered in dairy. ers realising the denaturation and the microparticulation of the whey proteins in the very same steps. The microparticles formed with LeanCream have an exceptionally high functionality, water Raw milk binding ability and when added back to the cheese milk they will stay trapped in the cheese curd (Steffl, 1999; Spiegel, 1999). Risk of bacteriophage However, since whey protein concentrate can potentially contain bacteriophage, it is important to control the phage by thermal treatment before adding it to the cheese milk in addition to the Whey protein particles Cheese milk general recommendations previously mentioned . The block flow Starter culture diagram of a typical cheese manufacturing plant Fig. 8 shows examples of the flow of whey in a typical facility. Thermal control The combination of time and temperature of the APV LeanCre- processing me™ technology is flexible and can easily be changed. Typical optimal holding time is 60 to 120 seconds and typical optimal Cheese Whey concentrate temperatures are in the range of 82°C to 88°C. As can be seen from fig. 7, the P008 phage are killed with a high log reduction under these heat treatment conditions. This Concentration Risk of bacteriophage complies fully with practical experience as SPX Flow Technology has no recorded cases of bacteriophage issues from microparticulated whey protein produced using APV LeanCreme™ Whey drainage Pasteurisation technology. It is not recommended to apply higher combination tempera- Whey Brining Risk of bacteriophage Risk of bacteriophage ture/time of denaturation as it it is known that the application of higher temperatures with the same range of holding time creates a different more compact structure of the microparticulated whey to the extent that less is incorporated into the cheese Cheese matrix. F I G . 8 . F LO W C H A R T O F A C H E E S E P R O C E S S I N W H I C H C O N C E N - Higher temperature would dramatically and irreversibly alter the whey microparticles high level of functional properties are T R AT E D W H E Y P R OT E I N S A R E B E I N G R E I N C O R P O R AT E D I N TO T H E C H E E S E M I L K T H E R M A L C O N T R O L O F W P C I S E S S E N T I A L TO AV O I D F E R M E N TAT I O N FA I L U R E S CA U S E D BY B A CT E R I O P H A G E . formed, e.g. high water binding ability, high creaminess perception and high level of incorporation in the dairy matrix (e.g. 2 2 0 0 6 - 0 3 - 1 1 - 2 01 2 - G B 11 R E FE R E NCE S Ackermann, H.-W. & DuBow, M. (1987), Viruses of Prokaryotes. IDF No. 308 (1995), Introduction to the theoretical and empiri- Boca Raton, Florida, CRC Press cal basis of the Danish cheese simulator (DCS)”, Bulletin of the Atamer et al. (2009), Screening for and characterization of International Dairy Federation Lactococcus lactis bacteriophage with high thermal resistance, Kessler, H. G. (2002), Food and Bio Process Engineering, Dairy Internattional Dairy Journal Technology, Verlag A.Kessler Bradley, D. E. (1967), Ultrastructure of and bacteriocins. Bacte- Madigan et al. (2000), Brock Biology of Microorganisms, ninth rial. Rev 31, p. 230-314 edition, published by Library of Congress Cataloging-in-Publica- Dogan et al., Food Micro (2008), Screening for new heat-re- tion Data sistant Lactococcal Bacteriphages in milk systems and determi- Müller-Merbach (2009), Lactococcus lactis bacteriophages in nation of the kinetics of inactivation. milk systems: Thermal-hydrostatic inactivation and proliteration http://en.wikipedia.org/wiki/Bacteriophage (28th April, 2010) http://en.wikipedia.org/wiki/Lytic_cycle (28th April, 2010) by means of propagation and diffusion VDI Verlag. Spiegel, T. (1999), Thermische Denaturierung und Aggregation von Milkenproteinen in Ultrafiltrationsmilkenkoncentraten http://www.mansfield.ohio-state.edu/~sabedon/beg_phage_ – Reaktionskinetik und Partikulieren im Schabewämetauscher. images.htm (28th April, 2010) Dissertation TU München-Weihenstephan, Freising ICTV (1982), The universal database of the International Com- Steffl, A. (1999), Integration von denaturierten Milkenproteinen mittee on Taxonomy and Viruses: http://www.ncbi.nlm.nih.gov. in die Matrix von Weichkäse. Dissertation, TU München-Weihen- ICTVdb/index.htm stephan Freising A B O U T S PX Based in Charlotte, North Carolina, SPX Corporation (NYSE: SPW) is a global Fortune 500 multi-industry manufacturing leader. For more information, please visit www.spx.com. S P X F L OW T E C H N O LO GY Pasteursvej DK-8600 Silkeborg, Denmark Phone: +45 70 278 278 Fax: +45 70 278 330 SPX reserves the right to incorporate our latest design and material changes without notice or obligation. Design features, materials of construction and dimensional data, as described in this bulletin, are provided for your information only and should not be relied upon unless confirmed in writing. Please contact your local sales representative for product availability in your region. For more information visit www.spx.com. The green “>” is a trademark of SPX Corporation, Inc.. ISSUED 11/2012 22006-03-11-2012-GB COPYRIGHT © 2010 SPX Corporation
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